Progress in RNA-Targeted Therapeutics for Human Diseases

Abstract

RNA-targeted therapy is reshaping molecular medicine by shifting the traditional “protein-centric” view toward an “RNA-regulatory network” paradigm. Beyond carrying genetic information, RNA plays essential roles in posttranscriptional regulation, signaling pathways, and epigenetic modulation. Advances in high-throughput sequencing, structural biology, and delivery technologies have accelerated the development of diverse RNA therapeutics, including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), microRNA (miRNA) modulators, messenger RNA (mRNA) therapeutics, aptamers, short hairpin RNA, and CRISPR/Cas-guided single-guide RNAs. However, a concise comparison of these major RNA modalities and the translational barriers that limit their broader clinical application is still lacking. This review outlines the mechanisms and representative applications of these RNA-based strategies in gene silencing, editing, protein replacement, immune activation, and targeted drug delivery. Special emphasis is placed on ASOs and siRNAs for neurological, metabolic, and infectious diseases, as well as mRNA therapeutics that are transforming vaccine development. Common challenges-such as in vivo stability, delivery efficiency, and immune activation-are also discussed. Finally, we highlight how chemical modification, nanotechnology, and artificial intelligence-assisted design are enhancing the specificity, stability, and safety of RNA therapeutics, providing a framework for advancing next-generation precision RNA medicine.

Keywords

antisense oligonucleotides / CRISPR/Cas9 / messenger RNA / RNA-targeted therapy / small interfering RNA

References

[1] Z. Su, M. Fang, A. Smolnikov, et al., “Post-transcriptional Regulation Supports the Homeostatic Expression of Mature RNA [J],” Briefings in Bioinformatics 26, no. 1 (2025): bbaf027.

[2] S. Xu, W. LI, J. Wu, et al., “The Role of miR-129-5p in Cancer: A Novel Therapeutic Target [J],” Current Molecular Pharmacology 15, no. 4 (2022): 647–657.

[3] D. Sandai, Z. Du, H. Zhang, and Q. Sun, “Regulatory Mechanisms and Emerging Diagnostic and Therapeutic Opportunities of Non-coding RNAs in Tumorigenesis: A Pan-cancer Perspective [J],” Critical Reviews in Clinical Laboratory Sciences (2025): 1–57.

[4] A. Xu, V. L. Kouznetsova, and I. F. Tsigelny, “Alzheimer's Disease Diagnostics Using mirna Biomarkers and Machine Learning [J],” Journal of Alzheimer's Disease 86, no. 2 (2022): 841–859.

[5] C.-W. Huang, W.-Z. Zhang, Y. Liao, et al., “A Targeted Approach: Gene and RNA Editing for Neurodegenerative Disease Treatment [J],” Life Sciences 376 (2025): 123756.

[6] Z. He, Y. Zhong, D. Hou, et al., “Integrated Analysis of mRNA-seq and miRNA-seq Reveals the Molecular Mechanism of the Intestinal Immune Response in Marsupenaeus japonicus Under Decapod Iridescent Virus 1 Infection [J],” Frontiers in Immunology 12 (2022): 807093.

[7] Y. Liu, W. Zhao, Z. Zhao, et al., “Hypoxia-anoikis-related Genes in LUAD: Machine Learning and RNA Sequencing Analysis of Immune Infiltration and Therapy Response [J],” American Journal of Cancer Research 15, no. 8 (2025): 3762.

[8] L. R. Baden, H. M. El Sahly, B. Essink, et al., “Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine [J],” New England Journal of Medicine 384, no. 5 (2021): 403–416.

[9] M. Arora, P. Bansal, and R. Singla, “RNA-based Therapeutics: Master Regulator for Bioengineering Systems in Medicine World [J],” Current Biotechnology 12, no. 2 (2023): 67–78.

[10] T. Vavilis, E. Stamoula, A. Ainatzoglou, et al., “mRNA in the Context of Protein Replacement Therapy [J],” Pharmaceutics 15, no. 1 (2023): 166.

[11] H. Zhang, D. Liu, K. Yang, et al., “Ionizable Guanidine-based Lipid Nanoparticle for Targeted mRNA Delivery and Cancer Immunotherapy [J],” Science Advances 11, no. 43 (2025): eadx5970.

[12] M. T. Aung-Htut, C. S. Mcintosh, K. A. Ham, et al., “Systematic Approach to Developing Splice Modulating Antisense Oligonucleotides [J],” International Journal of Molecular Sciences 20, no. 20 (2019): 5030.

[13] M. H. L. Slingsby, P. Vijey, I. T. Tsai, et al., “Sequence-specific 2'-O-methoxyethyl Antisense Oligonucleotides Activate human Platelets Through Glycoprotein VI, Triggering Formation of Platelet-leukocyte Aggregates [J],” Haematologica 107, no. 2 (2022): 519–531.

[14] D. Dhara, A. C. Hill, A. Ramesh, et al., “Synthesis, Biophysical and Biological Evaluation of Splice-Switching Oligonucleotides With Multiple LNA-Phosphothiotriester Backbones [J],” Journal of the American Chemical Society 146, no. 43 (2024): 29773–29781.

[15] M. Shin, P. Meda Krishnamurthy, G. Devi, et al., “Quantification of Antisense Oligonucleotides by Splint Ligation and Quantitative Polymerase Chain Reaction [J],” Nucleic Acid Therapeutics 32, no. 1 (2022): 66–73.

[16] J. Hu, X. Gong, Y. Fan, et al., “Modulation of Gene Expression in the Eye With Antisense Oligonucleotides [J],” Nucleic Acid Therapeutics 33, no. 6 (2023): 339–347.

[17] M. J. Tsai, R. A. I. Zambrano, J. L. Susas, et al., “Identifying Antisense Oligonucleotides to Disrupt Small RNA Regulated Antibiotic Resistance via a Cell-Free Transcription-Translation Platform [J],” ACS Synthetic Biology 12, no. 8 (2023): 2245–2251.

[18] Z. Chen, Y. Hu, X. Mao, et al., “Amphipathic Dendritic Poly-peptides Carrier to Deliver Antisense Oligonucleotides Against Multi-drug Resistant Bacteria in Vitro and in Vivo [J],” Journal of Nanobiotechnology 20, no. 1 (2022): 180.

[19] R. Mejzini, M. H. Caruthers, B. Schafer, et al., “Allele-Selective Thiomorpholino Antisense Oligonucleotides as a Therapeutic Approach for Fused-in-Sarcoma Amyotrophic Lateral Sclerosis [J],” International Journal of Molecular Sciences 25, no. 15 (2024): 8495.

[20] V. A. Korobeynikov, A. K. Lyashchenko, B. Blanco-Redondo, et al., “Antisense Oligonucleotide Silencing of FUS Expression as a Therapeutic Approach in Amyotrophic Lateral sclerosis [J],” Nature Medicine 28, no. 1 (2022): 104–116.

[21] B. Borges, S. M. Brown, W. J. Chen, et al., “Intra-amniotic Antisense Oligonucleotide Treatment Improves Phenotypes in Preclinical Models of Spinal Muscular Atrophy [J],” Science Translational Medicine 17, no. 798 (2025): eadv4656.

[22] J. Wang, J. Bai, S. Ouyang, et al., “Antisense Oligonucleotides Targeting the SMN2 Promoter Region Enhance SMN2 Expression in Spinal Muscular Atrophy Cell Lines and Mouse Model [J],” Human Molecular Genetics 31, no. 10 (2022): 1635–1650.

[23] T. A. Cole, H. Zhao, T. J. Collier, et al., “α-Synuclein Antisense Oligonucleotides as a Disease-modifying Therapy for Parkinson's Disease [J],” JCI Insight 6, no. 5 (2021): e135633.

[24] K. M. Tse, A. Vandenbon, X. Cui, et al., “Enhancement of Regnase-1 Expression With Stem Loop-targeting Antisense Oligonucleotides Alleviates Inflammatory Diseases [J],” Science Translational Medicine 14, no. 644 (2022): eabo2137.

[25] L. Huang, M. Aghajan, T. Quesenberry, et al., “Targeting Translation Termination Machinery With Antisense Oligonucleotides for Diseases Caused by Nonsense Mutations [J],” Nucleic Acid Therapeutics 29, no. 4 (2019): 175–186.

[26] Z. Chen, Z. Zhang, S. Liu, et al., “Synthesis and Evaluation of Antisense Oligonucleotides Prodrug With G-quadruplex Assembly and Lysosome Escape Capabilities for Oncotherapy [J],” Bioorganic Chemistry 148 (2024): 107475.

[27] T. Lu, C. Zhang, Z. Li, et al., “Human Angiotensin-converting Enzyme 2-specific Antisense Oligonucleotides Reduce Infection With SARS-CoV-2 Variants [J],” Journal of Allergy and Clinical Immunology 154, no. 4 (2024): 1044–1059.

[28] C. Tang, G. P. Hartley, C. Couillault, et al., “Preclinical Study and Parallel Phase II Trial Evaluating Antisense STAT3 Oligonucleotide and Checkpoint Blockade for Advanced Pancreatic, Non-small Cell Lung Cancer and Mismatch Repair-deficient Colorectal Cancer [J],” BMJ Oncology 3, no. 1 (2024): e000133.

[29] H. Zhang, Q. Yan, S. Jiang, et al., “Protein Post-translational Modifications and Tumor Immunity: A Pan-cancer Perspective [J],” Physics of Life Reviews 55 (2025): 142–209.

[30] A. Mata-Ventosa, A. Vila-Planas, A. Solsona-Pujol, et al., “RNase H-sensitive Multifunctional ASO-based Constructs as Promising Tools for the Treatment of Multifactorial Complex Pathologies [J],” Bioorganic Chemistry 150 (2024): 107595.

[31] N. El Boujnouni, M. L. Van Der Bent, M. Willemse, et al., “Block or Degrade? Balancing on- and off-target Effects of Antisense Strategies Against Transcripts With Expanded Triplet Repeats in DM1 [J],” Molecular Therapy Nucleic Acids 32 (2023): 622–636.

[32] H. Yasuhara, T. Yoshida, K. Sasaki, et al., “Reduction of off-Target Effects of Gapmer Antisense Oligonucleotides by Oligonucleotide Extension [J],” Molecular Diagnosis & Therapy 26, no. 1 (2022): 117–127.

[33] J. Scharner, W. K. Ma, Q. Zhang, et al., “Hybridization-mediated off-target Effects of Splice-switching Antisense Oligonucleotides [J],” Nucleic Acids Research 48, no. 2 (2020): 802–816.

[34] T. Yoshida, Y. Naito, H. Yasuhara, et al., “Evaluation of off-target Effects of Gapmer Antisense Oligonucleotides Using human Cells [J],” Genes to Cells 24, no. 12 (2019): 827–835.

[35] A. K. Iyer, K. M. Schoch, A. Verbeck, et al., “Targeted ASO-mediated Atp1a2 Knockdown in Astrocytes Reduces SOD1 Aggregation and Accelerates Disease Onset in Mutant SOD1 Mice [J],” PLoS ONE 18, no. 11 (2023): e0294731.

[36] E. Pandey and E. N. Harris, “Chloroquine and Cytosolic Galectins Affect Endosomal Escape of Antisense Oligonucleotides After Stabilin-mediated Endocytosis [J],” Molecular Therapy Nucleic Acids 33 (2023): 430–443.

[37] C. M. Miller, W. B. Wan, P. P. Seth, et al., “Endosomal Escape of Antisense Oligonucleotides Internalized by Stabilin Receptors Is Regulated by Rab5C and EEA1 during Endosomal Maturation [J],” Nucleic Acid Therapeutics 28, no. 2 (2018): 86–96.

[38] F. Bizot, A. Fayssoil, C. Gastaldi, et al., “Oligonucleotide Enhancing Compound Increases Tricyclo-DNA Mediated Exon-Skipping Efficacy in the Mdx Mouse Model [J],” Cells 12, no. 5 (2023): 702.

[39] X. H. Liang, H. Sun, C. W. Hsu, et al., “Golgi-endosome Transport Mediated by M6PR Facilitates Release of Antisense Oligonucleotides From Endosomes [J],” Nucleic Acids Research 48, no. 3 (2020): 1372–1391.

[40] E. L. Han, M. S. Padilla, R. Palanki, et al., “Predictive High-throughput Platform for Dual Screening of mRNA Lipid Nanoparticle Blood–brain Barrier Transfection and Crossing [J],” Nano Letters 24, no. 5 (2024): 1477–1486.

[41] J. Heredero, Á. Peña, E. Broset, et al., “Predictive Lung-and Spleen-Targeted mRNA Delivery With Biodegradable Ionizable Lipids in Four-Component LNPs [J],” Pharmaceutics 17, no. 4 (2025): 459.

[42] H. Tani, “Recent Advances and Prospects in RNA Drug Development [J],” International Journal of Molecular Sciences 25, no. 22 (2024): 12284.

[43] J. Wang, Y. Ding, K. Chong, et al., “Recent Advances in Lipid Nanoparticles and Their Safety Concerns for mRNA Delivery [J],” Vaccines 12, no. 10 (2024): 1148.

[44] S. A. E. El-Sayed, M. A. Rizk, H. Li, et al., “Preassembled Complexes of hAgo2 and ssRNA Delivered by Nanoparticles: A Novel Silencing Gene Expression Approach Overcoming the Absence of the Canonical Pathway of siRNA Processing in the Apicomplexan Parasite Babesia microti, Blood Parasite of Veterinary and Zoonotic Importance [J],” Emerging Microbes & Infections 14, no. 1 (2025): 2438658.

[45] D. Lessel, D. M. Zeitler, M. R. F. Reijnders, et al., “Germline AGO2 Mutations Impair RNA Interference and human Neurological Development [J],” Nature Communications 11, no. 1 (2020): 5797.

[46] C. Wang, W. Sheng, Y. Zhou, et al., “siRNA-AGO2 Complex Inhibits Bacterial Gene Translation: A Promising Therapeutic Strategy for Superbug Infection [J],” Cell Reports Medicine 6, no. 3 (2025): 101997.

[47] N. Javaid, T. W. Jang, Y. Fu, et al., “SFTSV NSs Interacts With AGO2 to Regulate the RNAi Pathway for Viral Replication [J],” Journal of Virology 99, no. 4 (2025): e0220524.

[48] S. Yamaguchi, M. Naganuma, T. Nishizawa, et al., “Structure of the Dicer-2-R2D2 Heterodimer Bound to a Small RNA Duplex [J],” Nature 607, no. 7918 (2022): 393–398.

[49] S. Petri, A. Dueck, G. Lehmann, et al., “Increased siRNA Duplex Stability Correlates With Reduced off-target and Elevated on-target Effects [J],” Rna 17, no. 4 (2011): 737–749.

[50] J. Li, C. Wu, W. Wang, et al., “Structurally Modulated Codelivery of siRNA and Argonaute 2 for Enhanced RNA Interference [J],” Proceedings of the National Academy of Sciences of the United States of America 115, no. 12 (2018): E2696–E2705.

[51] M. L. Vigh, S. Bressendorff, A. Thieffry, et al., “Nuclear and Cytoplasmic RNA Exosomes and PELOTA1 Prevent miRNA-induced Secondary siRNA Production in Arabidopsis [J],” Nucleic Acids Research 50, no. 3 (2022): 1396–1415.

[52] R. Zhang, Y. Jing, H. Zhang, et al., “Comprehensive Evolutionary Analysis of the Major RNA-Induced Silencing Complex Members [J],” Scientific Reports 8, no. 1 (2018): 14189.

[53] Z. Fu, X. Zhang, X. Zhou, et al., “In Vivo Self-assembled Small RNAs as a New Generation of RNAi Therapeutics [J],” Cell Research 31, no. 6 (2021): 631–648.

[54] R. S. Rosenson, D. Gaudet, R. A. Hegele, et al., “Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia [J],” New England Journal of Medicine 391, no. 10 (2024): 913–925.

[55] M. L. O'donoghue, R. S. Rosenson, B. Gencer, et al., “Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease [J],” New England Journal of Medicine 387, no. 20 (2022): 1855–1864.

[56] M. N. Saddique, M. Qadri, N. U. Ain, et al., “Safety and Effectiveness of Interference RNA (RNAi) Based Therapeutics in Cardiac Failure: A Systematic Review [J],” Heart & Lung 68 (2024): 298–304.

[57] S. Boutary, G. Khalaf, Y. Landesman, et al., “Therapeutic Potential of siRNA PMP22-SQ Nanoparticles for Charcot-Marie-Tooth 1A Neuropathy in Rodents and Non-human Primates [J],” International Journal of Pharmaceutics 671 (2025): 125234.

[58] K. Daman, J. Yan, A. Biscans, et al., “A Systemically Deliverable Lipid-conjugated siRNA Targeting DUX4 as an Facioscapulohumeral Muscular Dystrophy Therapeutic [J],” Molecular Therapy Methods & Clinical Development 33, no. 3 (2025): 101513.

[59] T. K. Sahu, A. K. S. Gurjar, P. K. Meher, et al., “Computational Insights Into RNAi-based Therapeutics for Foot and Mouth Disease of Bos taurus [J],” Scientific Reports 10, no. 1 (2020): 21593.

[60] M. Yang, F. Wang, H. Liang, et al., “Single-cell RNA Sequencing Reveals Distinct Immune Cell Subsets in Phalangeal and Soft-tissue Recurrence of Giant Cell Tumor of Bone [J],” Medicine Advances 1, no. 1 (2023): 14–29.

[61] H. Xu, S. Li, Y. Liu, et al., “A Novel pH-sensitive Nanoparticles Encapsulating Anti-PD-1 Antibody and MDK-siRNA Overcome Immune Checkpoint Blockade Resistance in HCC via Reshaping Immunosuppressive TME [J],” Journal of Experimental & Clinical Cancer Research 44, no. 1 (2025): 148.

[62] W. Kim, Z. Ye, V. Simonenko, et al., “Codelivery of TGFβ and Cox2 siRNA Inhibits HCC by Promoting T-cell Penetration Into the Tumor and Improves Response to Immune Checkpoint Inhibitors [J],” NAR Cancer 6, no. 1 (2024): zcad059.

[63] J. Du, Z. Que, A. Aihaiti, et al., “Co-delivery of SN38 and MEF2D-siRNA via tLyp-1-modified Liposomes Reverses PD-L1 Expression Induced by STING Activation in Hepatocellular Carcinoma [J],” Colloids and Surfaces B, Biointerfaces 245 (2025): 114318.

[64] X. Zhou, Y. Miao, Y. Wang, et al., “Tumour-derived Extracellular Vesicle Membrane Hybrid Lipid Nanovesicles Enhance siRNA Delivery by Tumour-homing and Intracellular Freeway Transportation [J],” Journal of Extracellular Vesicles 11, no. 3 (2022): e12198.

[65] J. Deng and H. Ke, “Overcoming the Resistance of Hepatocellular Carcinoma to PD-1/PD-L1 Inhibitor and the Resultant Immunosuppression by CD38 siRNA-loaded Extracellular Vesicles [J],” Oncoimmunology 12, no. 1 (2023): 2152635.

[66] J. Y. Wu, Z. X. Wang, G. Zhang, et al., “Targeted co-delivery of Beclin 1 siRNA and FTY720 to Hepatocellular Carcinoma by Calcium Phosphate Nanoparticles for Enhanced Anticancer Efficacy [J],” International Journal of Nanomedicine 13 (2018): 1265–1280.

[67] Y. Guo, F. Wang, S. Wan, et al., “Endothelium-targeted NF-κB siRNA Nanogel for Magnetic Resonance Imaging and Visualized-anti-inflammation Treatment of Atherosclerosis [J],” Biomaterials 314 (2025): 122897.

[68] J. Gao, K. Yu, Q. Luo, et al., “Near-Infrared II Fluorescence Imaging and Image-Guided siRNA Therapy of Atherosclerosis [J],” Journal of Medicinal Chemistry 67, no. 14 (2024): 12428–12438.

[69] L. Yang, Y. Chu, Y. Wang, et al., “siRNA-mediated Silencing of Wnt5a Regulates Inflammatory Responses in Atherosclerosis Through the MAPK/NF-κB Pathways [J],” International Journal of Molecular Medicine 34, no. 4 (2014): 1147–1152.

[70] H. Pan, R. U. Palekar, K. K. Hou, et al., “Anti-JNK2 Peptide-siRNA Nanostructures Improve Plaque Endothelium and Reduce Thrombotic Risk in Atherosclerotic Mice [J],” International Journal of Nanomedicine 13 (2018): 5187–5205.

[71] X. Wu, W. Liu, H. Jiang, et al., “Kindlin-2 siRNA Inhibits Vascular Smooth Muscle Cell Proliferation, Migration and Intimal Hyperplasia via Wnt Signaling [J],” International Journal of Molecular Medicine 37, no. 2 (2016): 436–444.

[72] H. Ni, H. Zhou, X. Liang, et al., “Reactive Oxygen Species-Responsive Nanoparticle Delivery of Small Interfering Ribonucleic Acid Targeting Olfactory Receptor 2 for Atherosclerosis Theranostics [J],” ACS Nano 18, no. 34 (2024): 23599–23614.

[73] Y. Wang, J. Zhou, Q. Yang, et al., “Therapeutic siRNA Targeting PLIN2 Ameliorates Steatosis, Inflammation, and Fibrosis in Steatotic Liver Disease Models [J],” Journal of Lipid Research 65, no. 10 (2024): 100635.

[74] W. Stewart, B. Hu, F. Li, et al., “A Combinatorial siRNA and mRNA Approach for Obesity Treatment Using Targeting Lipid Nanoparticles [J],” Journal of Controlled Release 383 (2025): 113857.

[75] J. Liang, W. Shao, P. Ni, et al., “siRNA/CS-PLGA Nanoparticle System Targeting Knockdown Intestinal SOAT2 Reduced Intestinal Lipid Uptake and Alleviated Obesity [J],” Advanced Science (Weinh) 11, no. 40 (2024): e2403442.

[76] M. S. Nestor, J. Hetzel, N. Awad, et al., “Novel Injectable Polypeptide Nanoparticle Encapsulated siRNA Targeting TGF-β1 and COX-2 for Localized Fat Reduction I: Preclinical in Vitro and Animal Models [J],” Journal of Cosmetic Dermatology 23, no. 10 (2024): 3133–3143.

[77] K. Taguchi, N. Bessho, M. Hida, et al., “Inactivation of MAPK in Epididymal Fat and Amelioration of Triglyceride Secretion by Injection of GRK2 siRNA in Ob/Ob Mice [J],” Naunyn-Schmiedebergs Archives of Pharmacology 391, no. 10 (2018): 1075–1083.

[78] P. S. Randeria, M. A. Seeger, X. Q. Wang, et al., “siRNA-based Spherical Nucleic Acids Reverse Impaired Wound Healing in Diabetic Mice by Ganglioside GM3 Synthase Knockdown [J],” Proceedings of the National Academy of Sciences of the United States of America 112, no. 18 (2015): 5573–5578.

[79] E. Şalva, S. Özbaş, S. Alan, et al., “Combination Therapy With Chitosan/siRNA Nanoplexes Targeting PDGF-D and PDGFR-β Reveals Anticancer Effect in Breast Cancer [J],” The Journal of Gene Medicine 25, no. 2 (2023): e3465.

[80] F. Li, Z. Zhu, M. Xue, et al., “siRNA-based Breast Cancer Therapy by Suppressing 17β-hydroxysteroid Dehydrogenase Type 1 in an Optimized Xenograft Cell and Molecular Biology Model in Vivo [J],” Drug Design, Development and Therapy 13 (2019): 757–766.

[81] J. Liang, S. Guo, M. Bai, et al., “Stimulus-responsive Hybrid Nanoparticles Based on Multiple Lipids for the co-delivery of Doxorubicin and Sphk2-siRNA and Breast Cancer Therapy [J],” Food and Chemical Toxicology 171 (2023): 113532.

[82] C. Zhang, W. Yuan, Y. Wu, et al., “Co-delivery of EGFR and BRD4 siRNA by Cell-penetrating Peptides-modified Redox-responsive Complex in Triple Negative Breast Cancer Cells [J],” Life Sciences 266 (2021): 118886.

[83] M. Jin, Y. Hou, X. Quan, et al., “Smart Polymeric Nanoparticles With pH-Responsive and PEG-Detachable Properties (II): Co-Delivery of Paclitaxel and VEGF siRNA for Synergistic Breast Cancer Therapy in Mice [J],” International Journal of Nanomedicine 16 (2021): 5479–5494.

[84] Z. Zhao, Y. Li, H. Liu, et al., “Co-delivery of IKBKE siRNA and Cabazitaxel by Hybrid Nanocomplex Inhibits Invasiveness and Growth of Triple-negative Breast Cancer [J],” Science Advances 6, no. 29 (2020): eabb0616.

[85] X. Yang, W. Yang, X. Xia, et al., “Intranasal Delivery of BACE1 siRNA and Rapamycin by Dual Targets Modified Nanoparticles for Alzheimer's Disease Therapy [J],” Small 18, no. 30 (2022): e2203182.

[86] Y. Zhou, F. Zhu, Y. Liu, et al., “Blood-brain Barrier-penetrating siRNA Nanomedicine for Alzheimer's Disease Therapy [J],” Science Advances 6, no. 41 (2020): eabc7031.

[87] M. Ferguson C, S. Hildebrand, B. Godinho, et al., “Silencing Apoe With Divalent-siRNAs Improves Amyloid Burden and Activates Immune Response Pathways in Alzheimer's Disease [J],” Alzheimer's & Dementia 20, no. 4 (2024): 2632–2652.

[88] Y. Geng, X. Long, Y. Zhang, et al., “FTO-targeted siRNA Delivery by MSC-derived Exosomes Synergistically Alleviates Dopaminergic Neuronal Death in Parkinson's disease via m6A-dependent Regulation of ATM mRNA [J],” Journal of Translational Medicine 21, no. 1 (2023): 652.

[89] L. Zhang, P. Chen, T. Chen, et al., “In Vivo Self-assembled siRNAs Within Small Extracellular Vesicles Attenuate LRRK2-induced Neurodegeneration in Parkinson's Disease Models [J],” Journal of Controlled Release 378 (2025): 1139–1153.

[90] W. Duan and H. Li, “Combination of NF-kB Targeted siRNA and Methotrexate in a Hybrid Nanocarrier towards the Effective Treatment in Rheumatoid Arthritis [J],” Journal of Nanobiotechnology 16, no. 1 (2018): 58.

[91] P. Khare, K. M. Dave, Y. S. Kamte, et al., “Development of Lipidoid Nanoparticles for siRNA Delivery to Neural Cells [J],” The Aaps Journal [Electronic Resource] 24, no. 1 (2021): 8.

[92] A. Biscans, A. Coles, R. Haraszti, et al., “Diverse Lipid Conjugates for Functional Extra-hepatic siRNA Delivery in Vivo [J],” Nucleic Acids Research 47, no. 3 (2019): 1082–1096.

[93] D. Guo, Y. Sun, J. Wu, et al., “Photoreceptor-targeted Extracellular Vesicles-mediated Delivery of Cul7 siRNA for Retinal Degeneration Therapy [J],” Theranostics 14, no. 13 (2024): 4916–4932.

[94] K. Uehara, T. Harumoto, A. Makino, et al., “Targeted Delivery to Macrophages and Dendritic Cells by Chemically Modified Mannose Ligand-conjugated siRNA [J],” Nucleic Acids Research 50, no. 9 (2022): 4840–4859.

[95] G. Li, Y. Zhang, and J. Li, “A Hybrid Nanoassembly for Ultrasound-inducible Cytosolic siRNA Delivery and Cancer Sono-gene Therapy [J],” Ultrasonics Sonochemistry 92 (2023): 106262.

[96] A. Biscans, J. Caiazzi, N. Mchugh, et al., “Docosanoic Acid Conjugation to siRNA Enables Functional and Safe Delivery to Skeletal and Cardiac Muscles [J],” Molecular Therapy 29, no. 4 (2021): 1382–1394.

[97] X. Zeng, D. Nie, Z. Liu, et al., “Aptamer sgc8-Modified PAMAM Nanoparticles for Targeted siRNA Delivery to Inhibit BCL11B in T-Cell Acute Lymphoblastic Leukemia [J],” International Journal of Nanomedicine 19 (2024): 12297–12309.

[98] A. Jonczyk, M. Gottschalk, M. S. J. Mangan, et al., “Topical Application of a CCL22-binding Aptamer Suppresses Contact Allergy [J],” Molecular Therapy Nucleic Acids 35, no. 3 (2024): 102254.

[99] H. J. Kim, H. J. Sung, Y. M. Lee, et al., “Therapeutic Application of Drug-Conjugated HER2 Oligobody (HER2-DOligobody) [J],” International Journal of Molecular Sciences 21, no. 9 (2020): 3286.

[100] J. Yan, R. Bhadane, M. Ran, et al., “Development of Aptamer-DNAzyme Based Metal-nucleic Acid Frameworks for Gastric Cancer Therapy [J],” Nature Communications 15, no. 1 (2024): 3684.

[101] L. Zhu, J. Yuhan, H. Yu, et al., “Aptamer Functionalized Nucleic Acid Nano Drug for Targeted Synergistic Therapy for Colon Cancer [J],” Journal of Nanobiotechnology 21, no. 1 (2023): 182.

[102] L. Zhang, L. Li, X. Wang, et al., “Development of a Novel PROTAC Using the Nucleic Acid Aptamer as a Targeting Ligand for Tumor Selective Degradation of Nucleolin [J],” Molecular Therapy Nucleic Acids 30 (2022): 66–79.

[103] P. Zhou, S. Zhang, L. Li, et al., “Targeted Degradation of VEGF With Bispecific Aptamer-based LYTACs Ameliorates Pathological Retinal Angiogenesis [J],” Theranostics 14, no. 13 (2024): 4983–5000.

[104] Y. Xiao, T. Pan, W. Da, et al., “Aptamer-drug Conjugates-loaded Bacteria for Pancreatic Cancer Synergistic Therapy [J],” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 272.

[105] N. Zhao, Z. Zeng, and Y. Zu, “Self-Assembled Aptamer-Nanomedicine for Targeted Chemotherapy and Gene Therapy [J],” Small 14, no. 4 (2018).

[106] E. Esawi, W. Alshaer, I. S. Mahmoud, et al., “Aptamer-Aptamer Chimera for Targeted Delivery and ATP-Responsive Release of Doxorubicin Into Cancer Cells [J],” International Journal of Molecular Sciences 22, no. 23 (2021): 12940.

[107] B. Powell Gray, X. Song, D. S. Hsu, et al., “An Aptamer for Broad Cancer Targeting and Therapy [J],” Cancers (Basel) 12, no. 11 (2020): 3217.

[108] C. Zhou, Z. Luo, Z. Zhang, et al., “Screening and Identification of Novel DNA Aptamer for Targeted Delivery to Injured Podocytes in Glomerular Diseases [J],” Advanced Science (Weinh) 12, no. 20 (2025): e2412356.

[109] M. W. Helal, M. M. Faried, S. M. Salah, et al., “Comparative Analysis of Aptamer-Conjugated Chemical and Green Synthesized Gold Nanoparticles for Targeted Therapy in MCF-7 Cancer Cells [J],” Applied Biochemistry and Biotechnology 197, no. 3 (2025): 1678–1695.

[110] F. Qiu, D. Xie, H. Chen, et al., “Generation of Cytotoxic Aptamers Specifically Targeting Fibroblast-Like Synoviocytes by CSCT-SELEX for Treatment of Rheumatoid Arthritis [J],” Annals of the Rheumatic Diseases 84, no. 5 (2025): 726–745.

[111] G. Wu, C. Liu, B. Cao, et al., “Connective Tissue Growth Factor-targeting DNA Aptamer Suppresses Pannus Formation as Diagnostics and Therapeutics for Rheumatoid Arthritis [J],” Frontiers in Immunology 13 (2022): 934061.

[112] T. Matsui, Y. Higashimoto, Y. Nishino, et al., “RAGE-Aptamer Blocks the Development and Progression of Experimental Diabetic Nephropathy [J],” Diabetes 66, no. 6 (2017): 1683–1695.

[113] D. Benigno, N. Navarro, A. Aviñó, et al., “Aptamer-Drug Conjugates for a Targeted and Synergistic Anticancer Response: Exploiting T30923-5-fluoro-2'-deoxyuridine (INT-FdU) Derivatives [J],” European Journal of Pharmaceutics and Biopharmaceutics 201 (2024): 114354.

[114] A. Clua, C. Fàbrega, J. García-Chica, et al., “Parallel G-quadruplex Structures Increase Cellular Uptake and Cytotoxicity of 5-Fluoro-2'-deoxyuridine Oligomers in 5-Fluorouracil Resistant Cells [J],” Molecules (Basel, Switzerland) 26, no. 6 (2021): 1741.

[115] Y. Tabuchi, J. Yang, and M. Taki, “Relative Nuclease Resistance of a DNA Aptamer Covalently Conjugated to a Target Protein [J],” International Journal of Molecular Sciences 23, no. 14 (2022): 7778.

[116] J. M. Harp, D. C. Guenther, A. Bisbe, et al., “Structural Basis for the Synergy of 4'- and 2'-modifications on siRNA Nuclease Resistance, Thermal Stability and RNAi Activity [J],” Nucleic Acids Research 46, no. 16 (2018): 8090–8104.

[117] A. Caliendo, S. Camorani, L. E. Ibarra, et al., “A Novel CD44-targeting Aptamer Recognizes Chemoresistant Mesenchymal Stem-Like TNBC Cells and Inhibits Tumor Growth [J],” Bioactive Materials 50 (2025): 443–460.

[118] R. Baek, K. Coughlan, L. Jiang, et al., “Characterizing the Mechanism of Action for mRNA Therapeutics for the Treatment of Propionic Acidemia, Methylmalonic Acidemia, and Phenylketonuria [J],” Nature Communications 15, no. 1 (2024): 3804.

[119] E. C. Mollocana-Lara, M. Ni, S. N. Agathos, et al., “The Infinite Possibilities of RNA Therapeutics [J],” Journal of Industrial Microbiology & Biotechnology 48, no. 9-10 (2021): kuab063.

[120] R. A. Meyer, G. P. Hussmann, N. C. Peterson, et al., “A Scalable and Robust Cationic Lipid/Polymer Hybrid Nanoparticle Platform for mRNA Delivery [J],” International Journal of Pharmaceutics 611 (2022): 121314.

[121] Y. Li, Y. Liao, Y. Miao, et al., “Interleukin-35 mRNA Therapy for Influenza Virus-induced Pneumonia in Mice [J],” European Journal of Pharmacology 993 (2025): 177366.

[122] L. Arrizabalaga, C. A. Di Trani, M. Fernández-Sendin, et al., “Intraperitoneal Administration of mRNA Encoding Interleukin-12 for Immunotherapy in Peritoneal Carcinomatosis [J],” Journal of Nanobiotechnology 23, no. 1 (2025): 113.

[123] S. Meulewaeter, G. Nuytten, M. H. Y. Cheng, et al., “Continuous Freeze-drying of Messenger RNA Lipid Nanoparticles Enables Storage at Higher Temperatures [J],” Journal of Controlled Release 357 (2023): 149–160.

[124] J. Lei, S. Qi, X. Yu, et al., “Development of Mannosylated Lipid Nanoparticles for mRNA Cancer Vaccine With High Antigen Presentation Efficiency and Immunomodulatory Capability [J],” Angewandte Chemie (International ed in English) 63, no. 13 (2024): e202318515.

[125] X. Zhang, K. Men, Y. Zhang, et al., “Local and Systemic Delivery of mRNA Encoding Survivin-T34A by lipoplex for Efficient Colon Cancer Gene Therapy [J],” International Journal of Nanomedicine 14 (2019): 2733–2751.

[126] Z. Zhang, B. Ma, B. Li, et al., “Cardiolipin-mimic Lipid Nanoparticles Without Antibody Modification Delivered Senolytic in Vivo CAR-T Therapy for Inflamm-aging [J],” Cell Reports Medicine 6, no. 7 (2025): 102209.

[127] M. B. Finn, T. A. Penfound, S. Salehi, et al., “Immunogenicity of a 30-valent M Protein mRNA Group A Streptococcus Vaccine [J],” Vaccine 42, no. 22 (2024): 126205.

[128] Q. Cheng, T. Wei, L. Farbiak, et al., “Selective Organ Targeting (SORT) Nanoparticles for Tissue-specific mRNA Delivery and CRISPR-Cas Gene Editing [J],” Nature Nanotechnology 15, no. 4 (2020): 313–320.

[129] X. Huang, C. Liu, S. N. Sharma, et al., “Oral Delivery of Liquid mRNA Therapeutics by an Engineered Capsule for Treatment of Preclinical Intestinal Disease [J],” Science Translational Medicine 17, no. 807 (2025): eadu1493.

[130] M. Qiu, Y. Tang, J. Chen, et al., “Lung-selective mRNA Delivery of Synthetic Lipid Nanoparticles for the Treatment of Pulmonary Lymphangioleiomyomatosis [J],” Proceedings of the National Academy of Sciences of the United States of America 119, no. 8 (2022): e2116271119.

[131] Y. Xue, C. Wang, H. Li, et al., “Lipid Nanoparticles Enhance mRNA Delivery to the Central Nervous System Upon Intrathecal Injection [J],” Advanced Materials 37, no. 27 (2025): e2417097.

[132] T. Fan, C. Xu, J. Wu, et al., “Lipopolyplex-formulated mRNA Cancer Vaccine Elicits Strong Neoantigen-specific T Cell Responses and Antitumor Activity [J],” Science Advances 10, no. 41 (2024): eadn9961.

[133] Y. Wang, Y. Peng, G. Zi, et al., “Co-delivery of Cas9 mRNA and Guide RNAs for Editing of LGMN Gene Represses Breast Cancer Cell Metastasis [J],” Scientific Reports 14, no. 1 (2024): 8095.

[134] J. Yu, Q. Li, C. Zhang, et al., “Targeted LNPs Deliver IL-15 Superagonists mRNA for Precision Cancer Therapy [J],” Biomaterials 317 (2025): 123047.

[135] S. Ma, X. Li, Y. Mai, et al., “Immunotherapeutic Treatment of Lung Cancer and Bone Metastasis With a mPLA/mRNA Tumor Vaccine [J],” Acta Biomaterialia 169 (2023): 489–499.

[136] M. A. Hoffmann, Z. Yang, K. E. Huey-Tubman, et al., “ESCRT Recruitment to SARS-CoV-2 Spike Induces Virus-Like Particles That Improve mRNA Vaccines [J],” Cell 186, no. 11 (2023): 2380–2391.e9.

[137] N. Lasrado, M. Rowe, K. Mcmahan, et al., “SARS-CoV-2 XBB. 1.5 mRNA Booster Vaccination Elicits Limited Mucosal Immunity [J],” Science Translational Medicine 16, no. 770 (2024): eadp8920.

[138] Y. Niu, W. Quan, Y. Li, et al., “Internal Drivers of the Global Pandemic of the Omicron Variants of SARS-CoV-2 [J],” Medicine Advances 2, no. 3 (2024): 262–273.

[139] L. A. Rojas, Z. Sethna, K. C. Soares, et al., “Personalized RNA Neoantigen Vaccines Stimulate T Cells in Pancreatic Cancer [J],” Nature 618, no. 7963 (2023): 144–150.

[140] J. Chen, Z. Ye, C. Huang, et al., “Lipid Nanoparticle-mediated Lymph Node-targeting Delivery of mRNA Cancer Vaccine Elicits Robust CD8(+) T Cell Response [J],” Proceedings of the National Academy of Sciences of the United States of America 119, no. 34 (2022): e2207841119.

[141] J. Wang, Q. Wang, L. Ma, et al., “Development of an mRNA-based Therapeutic Vaccine mHTV-03E2 for High-risk HPV-related Malignancies [J],” Molecular Therapy 32, no. 7 (2024): 2340–2356.

[142] M. G. Alameh, A. Semon, N. U. Bayard, et al., “A Multivalent mRNA-LNP Vaccine Protects Against Clostridioides difficile Infection [J],” Science 386, no. 6717 (2024): 69–75.

[143] Z. Luo, Y. Lin, Y. Meng, et al., “Spleen-Targeted mRNA Vaccine Doped With Manganese Adjuvant for Robust Anticancer Immunity in Vivo [J],” ACS Nano 18, no. 44 (2024): 30701–30715.

[144] Z. Sethna, P. Guasp, C. Reiche, et al., “RNA Neoantigen Vaccines Prime Long-lived CD8(+) T Cells in Pancreatic Cancer [J],” Nature 639, no. 8056 (2025): 1042–1051.

[145] G. Cafri, J. J. Gartner, T. Zaks, et al., “mRNA Vaccine-induced Neoantigen-specific T Cell Immunity in Patients With Gastrointestinal Cancer [J],” Journal of Clinical Investigation 130, no. 11 (2020): 5976–5988.

[146] M. Pine, G. Arora, T. M. Hart, et al., “Development of an mRNA-lipid Nanoparticle Vaccine Against Lyme Disease [J],” Molecular Therapy 31, no. 9 (2023): 2702–2714.

[147] A. Suberi, M. K. Grun, T. Mao, et al., “Polymer Nanoparticles Deliver mRNA to the Lung for Mucosal Vaccination [J],” Science Translational Medicine 15, no. 709 (2023): eabq0603.

[148] Z. Tang, X. You, Y. Xiao, et al., “Inhaled mRNA Nanoparticles Dual-targeting Cancer Cells and Macrophages in the Lung for Effective Transfection [J],” Proceedings of the National Academy of Sciences of the United States of America 120, no. 44 (2023): e2304966120.

[149] Z. Xie, Y. C. Lin, J. M. Steichen, et al., “mRNA-LNP HIV-1 Trimer Boosters Elicit Precursors to Broad Neutralizing Antibodies [J],” Science 384, no. 6697 (2024): eadk0582.

[150] R. Wang, Y. Zhang, S. Du, et al., “Nanoformulations Downregulating METTL16 Combined With mRNA Tumor Vaccines Suppress Triple-Negative Breast Cancer and Prevent Metastasis [J],” International Journal of Nanomedicine 20 (2025): 8951–8966.

[151] A. Vasukutty, S. Chahal, K. H. Lee, et al., “Dual-Mechanism mRNA Delivery via Fluorinated-Sorbitol Polyplexes: Enhancing Cellular Uptake and Endosomal Escape for COVID-19 Vaccination [J],” Advanced Healthcare Materials 14, no. 6 (2025): e2403374.

[152] J. Chung D, S. Sharma, M. Rangesa, et al., “Langerhans Dendritic Cell Vaccine Bearing mRNA-encoded Tumor Antigens Induces Antimyeloma Immunity After Autotransplant [J],” Blood Advances 6, no. 5 (2022): 1547–1558.

[153] M. Broketa, A. Sokal, M. Mor, et al., “Qualitative Monitoring of SARS-CoV-2 mRNA Vaccination in Humans Using Droplet Microfluidics [J],” JCI Insight 8, no. 13 (2023): e166602.

[154] L. Xue, G. Zhao, N. Gong, et al., “Combinatorial Design of Siloxane-incorporated Lipid Nanoparticles Augments Intracellular Processing for Tissue-specific mRNA Therapeutic Delivery [J],” Nature Nanotechnology 20, no. 1 (2025): 132–143.

[155] Z. Wang, F. Muecksch, R. Raspe, et al., “Memory B Cell Development Elicited by mRNA Booster Vaccinations in the Elderly [J],” Journal of Experimental Medicine 220, no. 9 (2023): e20230668.

[156] E. M. Stevenson, S. Terry, D. Copertino, et al., “SARS CoV-2 mRNA Vaccination Exposes Latent HIV to Nef-specific CD8(+) T-cells [J],” Nature Communications 13, no. 1 (2022): 4888.

[157] L. Zhang, J. Bai, A. Shen, et al., “Artificially Tagging Tumors With Nano-aluminum Adjuvant-tethered Antigen mRNA Recruits and Activates Antigen-specific Cytotoxic T Cells for Enhanced Cancer Immunotherapy [J],” Biomaterials 317 (2025): 123085.

[158] P. Chen, X. He, Y. Hu, et al., “Spleen-Targeted mRNA Delivery by Amphiphilic Carbon Dots for Tumor Immunotherapy [J],” ACS Applied Materials & Interfaces 15, no. 16 (2023): 19937–19950.

[159] F. Cao, Y. Xu, Y. Guan, et al., “Enhancing the Potency of 5T4 mRNA Vaccine by CD70 mRNA-LNPs Through ADCC and T Cell Boosting in Prostate Cancer Therapy [J],” Journal of Nanobiotechnology 23, no. 1 (2025): 523.

[160] C. T. T. Le, K. H. Kim, J. R. Raha, et al., “Dual Roles of influenza B Virus Neuraminidase mRNA Vaccine in Enhancing Cross-lineage Protection by Supplementing Inactivated Split Vaccination [J],” Journal of Virology 99, no. 5 (2025): e0229424.

[161] X. Li, L. Ma, J. Guo, et al., “Synergistic Anti-tumor Effects of mRNA Vaccine and PERK Inhibitor Combination in Melanoma Treatment [J],” Colloids and Surfaces B, Biointerfaces 254 (2025): 114808.

[162] W. Zheng, L. Wang, S. Geng, et al., “CircMIB2 therapy Can Effectively Treat Pathogenic Infection by Encoding a Novel Protein [J],” Cell Death & Disease 14, no. 8 (2023): 578.

[163] J. D. Kelly, K. J. Hoggatt, N. C. Lo, et al., “Annual Variant-Targeted Vaccination to Prevent Severe COVID-19 in Cohorts with Vaccine-Derived and Hybrid Immunity [J],” Clinical Infectious Diseases 81, no. 2 (2025): 222–230.

[164] E. Su, S. Fischer, R. Demmer-Steingruber, et al., “Humoral and Cellular Responses to mRNA-based COVID-19 Booster Vaccinations in Patients With Solid Neoplasms Under Active Treatment [J],” ESMO Open 7, no. 5 (2022): 100587.

[165] T. Buttiron Webber, N. Provinciali, I. M. Briata, et al., “Predictors of Poor Seroconversion and Adverse Events to SARS-CoV-2 mRNA BNT162b2 Vaccine in Cancer Patients on Active Treatment. Role of the Research Nurse [J],” Professioni Infermieristiche 74, no. 4 (2021): 261.

[166] W. Li, Y. Li, J. Li, et al., “All-Trans-Retinoic Acid-Adjuvanted mRNA Vaccine Induces Mucosal Anti-Tumor Immune Responses for Treating Colorectal Cancer [J],” Advanced Science (Weinh) 11, no. 22 (2024): e2309770.

[167] J. Wan, Z. Wang, L. Wang, et al., “Circular RNA Vaccines With Long-term Lymph Node-targeting Delivery Stability After Lyophilization Induce Potent and Persistent Immune Responses [J],” MBio 15, no. 1 (2024): e0177523.

[168] R. A. Wesselhoeft, P. S. Kowalski, F. C. Parker-Hale, et al., “RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration in Vivo [J],” Molecular Cell 74, no. 3 (2019): 508–520.e4.

[169] Y. Kawaguchi, M. Kimura, T. Karaki, et al., “Modulating Immunogenicity and Reactogenicity in mRNA-Lipid Nanoparticle Vaccines Through Lipid Component Optimization [J],” ACS Nano 19, no. 30 (2025): 27977–28001.

[170] A. Valentin, C. Bergamaschi, M. Rosati, et al., “Comparative Immunogenicity of an mRNA/LNP and a DNA Vaccine Targeting HIV Gag Conserved Elements in Macaques [J],” Frontiers in Immunology 13 (2022): 945706.

[171] J. Xu, Y. Ren, J. Lu, et al., “Genome-wide Profiling of N6-methyladenosine-modified Pseudogene-derived Long Noncoding RNAs Reveals the Tumour-promoting and Innate Immune-restraining Function of RPS15AP12 in Ovarian Cancer [J],” Clinical and Translational Medicine 15, no. 3 (2025): e70249.

[172] J. B. Case, A. W. Ashbrook, T. S. Dermody, et al., “Mutagenesis of S-Adenosyl-l-Methionine-Binding Residues in Coronavirus nsp14 N7-Methyltransferase Demonstrates Differing Requirements for Genome Translation and Resistance to Innate Immunity [J],” Journal of Virology 90, no. 16 (2016): 7248–7256.

[173] J. Xu, Y. Cai, Z. Ma, et al., “The RNA Helicase DDX5 Promotes Viral Infection via Regulating N6-methyladenosine Levels on the DHX58 and NFκB Transcripts to Dampen Antiviral Innate Immunity [J],” Plos Pathogens 17, no. 4 (2021): e1009530.

[174] S. L. Lin and S. Y. Ying, “Gene Silencing in Vitro and in Vivo Using Intronic MicroRNAs [J],” Methods in Molecular Biology 1733 (2018): 107–126.

[175] L. Zong, Y. Zhu, R. Liang, et al., “Gap Junction Mediated miRNA Intercellular Transfer and Gene Regulation: A Novel Mechanism for Intercellular Genetic Communication [J],” Scientific Reports 6 (2016): 19884.

[176] E. Matsuura-Suzuki, K. Kiyokawa, S. Iwasaki, et al., “miRNA-mediated Gene Silencing in Drosophila Larval Development Involves GW182-dependent and Independent Mechanisms [J],” The EMBO Journal 43, no. 23 (2024): 6161–6179.

[177] S. Djuranovic, A. Nahvi, and R. Green, “miRNA-mediated Gene Silencing by Translational Repression Followed by mRNA Deadenylation and Decay [J],” Science 336, no. 6078 (2012): 237–240.

[178] M. Sun, J. Ding, D. Li, et al., “NUDT21 regulates 3'-UTR Length and microRNA-mediated Gene Silencing in Hepatocellular Carcinoma [J],” Cancer Letters 410 (2017): 158–168.

[179] Y. Yan, M. Acevedo, L. Mignacca, et al., “The Sequence Features That Define Efficient and Specific hAGO2-dependent miRNA Silencing Guides [J],” Nucleic Acids Research 46, no. 16 (2018): 8181–8196.

[180] J. Kim, M. Muraoka, H. Okada, et al., “The RNA Helicase DDX6 Controls Early Mouse Embryogenesis by Repressing Aberrant Inhibition of BMP Signaling Through miRNA-mediated Gene Silencing [J],” Plos Genetics 18, no. 10 (2022): e1009967.

[181] F. Llorens, K. Thüne, E. Martí, et al., “Regional and Subtype-dependent miRNA Signatures in Sporadic Creutzfeldt-Jakob Disease Are Accompanied by Alterations in miRNA Silencing Machinery and Biogenesis [J],” Plos Pathogens 14, no. 1 (2018): e1006802.

[182] R. Panella, A. Petri, B. N. Desai, et al., “MicroRNA-22 Is a Key Regulator of Lipid and Metabolic Homeostasis [J],” International Journal of Molecular Sciences 24, no. 16 (2023): 12870.

[183] M. Thibonnier, C. Esau, S. Ghosh, et al., “Metabolic and Energetic Benefits of microRNA-22 Inhibition [J],” BMJ Open Diabetes Research & Care 8, no. 1 (2020): e001478.

[184] Y. Shen, L. Cheng, M. Xu, et al., “SGLT2 inhibitor Empagliflozin Downregulates miRNA-34a-5p and Targets GREM2 to Inactivate Hepatic Stellate Cells and Ameliorate Non-alcoholic Fatty Liver Disease-associated Fibrosis [J],” Metabolism 146 (2023): 155657.

[185] J. Zhu, B. Liu, Z. Wang, et al., “Exosomes From Nicotine-stimulated Macrophages Accelerate Atherosclerosis Through miR-21-3p/PTEN-mediated VSMC Migration and Proliferation [J],” Theranostics 9, no. 23 (2019): 6901–6919.

[186] P. González-López, M. Álvarez-Villarreal, R. Ruiz-Simón, et al., “Role of miR-15a-5p and miR-199a-3p in the Inflammatory Pathway Regulated by NF-κB in Experimental and human Atherosclerosis [J],” Clinical and Translational Medicine 13, no. 8 (2023): e1363.

[187] X. Lu, B. Yang, H. Yang, et al., “MicroRNA-320b Modulates Cholesterol Efflux and Atherosclerosis [J],” Journal of Atherosclerosis and Thrombosis 29, no. 2 (2022): 200–220.

[188] Y. Liu, Y. Wu, C. Wang, et al., “MiR-127-3p Enhances Macrophagic Proliferation via Disturbing Fatty Acid Profiles and Oxidative Phosphorylation in Atherosclerosis [J],” Journal of Molecular and Cellular Cardiology 193 (2024): 36–52.

[189] Y. Zhu, S. Ren, H. Huang, et al., “Restoration of miR-299-3p Promotes Efferocytosis and Ameliorates Atherosclerosis via Repressing CD47 in Mice [J],” FASEB Journal 38, no. 15 (2024): e23857.

[190] W. Li, Y. Li, F. Jiang, et al., “Correlation Between Serum Levels of microRNA-21 and Inflammatory Factors in Patients With Chronic Heart Failure [J],” Medicine 101, no. 38 (2022): e30596.

[191] H. Zhou, P. Liu, X. Guo, et al., “Fibroblast-derived miR-425-5p Alleviates Cardiac Remodelling in Heart Failure via Inhibiting the TGF-β1/Smad Signalling [J],” Journal of Cellular and Molecular Medicine 28, no. 21 (2024): e70199.

[192] K. L. Jackson, C. Gueguen, K. Lim, et al., “Neural Suppression of miRNA-181a in the Kidney Elevates Renin Expression and Exacerbates Hypertension in Schlager Mice [J],” Hypertension Research 43, no. 11 (2020): 1152–1164.

[193] R. Nosalski, M. Siedlinski, L. Denby, et al., “T-Cell-Derived miRNA-214 Mediates Perivascular Fibrosis in Hypertension [J],” Circulation Research 126, no. 8 (2020): 988–1003.

[194] Q. Zhao, H. Sun, L. Yin, et al., “miR‑126a‑5p‑Dbp and miR‑31a‑Crot/Mrpl4 Interaction Pairs Crucial for the Development of Hypertension and Stroke [J],” Molecular Medicine Reports 20, no. 5 (2019): 4151–4167.

[195] H. Zhang, A. Laux, K. R. Stenmark, et al., “Mechanisms Contributing to the Dysregulation of miRNA-124 in Pulmonary Hypertension [J],” International Journal of Molecular Sciences 22, no. 8 (2021): 3852.

[196] Y. Liu, G. Liu, H. Zhang, et al., “MiRNA-199a-5p Influences Pulmonary Artery Hypertension via Downregulating Smad3 [J],” Biochemical and Biophysical Research Communications 473, no. 4 (2016): 859–866.

[197] S. Zhang, M. Xing, G. Chen, et al., “Up-regulation of miR-335 and miR-674-3p in the Rostral Ventrolateral Medulla Contributes to Stress-induced Hypertension [J],” Journal of Neurochemistry 161, no. 5 (2022): 387–404.

[198] Y. Zhang, X. Le, S. Zheng, et al., “MicroRNA-146a-5p-modified human Umbilical Cord Mesenchymal Stem Cells Enhance Protection Against Diabetic Nephropathy in Rats Through Facilitating M2 Macrophage Polarization [J],” Stem Cell Research & Therapy 13, no. 1 (2022): 171.

[199] S. Veitch, M. S. Njock, M. Chandy, et al., “MiR-30 Promotes Fatty Acid Beta-oxidation and Endothelial Cell Dysfunction and Is a Circulating Biomarker of Coronary Microvascular Dysfunction in Pre-clinical Models of Diabetes [J],” Cardiovascular Diabetology 21, no. 1 (2022): 31.

[200] Y. D. Wang, L. L. Wu, Y. N. Mai, et al., “miR-32-5p Induces Hepatic Steatosis and Hyperlipidemia by Triggering De Novo Lipogenesis [J],” Metabolism 146 (2023): 155660.

[201] T. A. Phu, N. K. Vu, M. Ng, et al., “ApoE Enhances Mitochondrial Metabolism via microRNA-142a/146a-regulated Circuits That Suppress Hematopoiesis and Inflammation in Hyperlipidemia [J],” Cell Reports 42, no. 10 (2023): 113206.

[202] H. Chen, J. Gao, Q. Xu, et al., “MiR-145-5p Modulates Lipid Metabolism and M2 Macrophage Polarization by Targeting PAK7 and Regulating β-catenin Signaling in Hyperlipidemia [J],” Canadian Journal of Physiology and Pharmacology 99, no. 9 (2021): 857–863.

[203] H. Zhao and Y. Li, “Upregulated MicroRNA-185-3p Inhibits the Development of Hyperlipidemia in Rats [J],” Kidney & Blood Pressure Research 48, no. 1 (2023): 35–44.

[204] T. Zhang, H. Shi, N. Liu, et al., “Activation of microRNA-378a-3p Biogenesis Promotes Hepatic Secretion of VLDL and Hyperlipidemia by Modulating ApoB100-Sortilin1 Axis [J],” Theranostics 10, no. 9 (2020): 3952–3966.

[205] Y. Ning, P. Huang, G. Chen, et al., “Atorvastatin-pretreated Mesenchymal Stem Cell-derived Extracellular Vesicles Promote Cardiac Repair After Myocardial Infarction via Shifting Macrophage Polarization by Targeting microRNA-139-3p/Stat1 Pathway [J],” BMC Medicine [Electronic Resource] 21, no. 1 (2023): 96.

[206] J. Gu, J. You, H. Liang, et al., “Engineered Bone Marrow Mesenchymal Stem Cell-derived Exosomes Loaded With miR302 Through the Cardiomyocyte Specific Peptide Can Reduce Myocardial Ischemia and Reperfusion (I/R) Injury [J],” Journal of Translational Medicine 22, no. 1 (2024): 168.

[207] Q. Yu, Y. Li, N. Zhang, et al., “Silencing of lncRNA NEAT1 Alleviates Acute Myocardial Infarction by Suppressing miR-450-5p/ACSL4-mediated Ferroptosis [J],” Experimental Cell Research 442, no. 2 (2024): 114217.

[208] L. Yan, N. Guo, Y. Cao, et al., “miRNA‑145 Inhibits Myocardial Infarction‑Induced Apoptosis Through Autophagy via Akt3/mTOR Signaling Pathway in Vitro and in Vivo [J],” International Journal of Molecular Medicine 42, no. 3 (2018): 1537–1547.

[209] T. Wang, T. Li, X. Niu, et al., “ADSC-derived Exosomes Attenuate Myocardial Infarction Injury by Promoting miR-205-mediated Cardiac Angiogenesis [J],” Biology Direct 18, no. 1 (2023): 6.

[210] F. Zhou, W. D. Fu, and L. Chen, “MiRNA-182 Regulates the Cardiomyocyte Apoptosis in Heart Failure [J],” European Review for Medical and Pharmacological Sciences 23, no. 11 (2019): 4917–4923.

[211] L. Tan, D. Xiong, H. Zhang, et al., “ETS2 promotes Cardiomyocyte Apoptosis and Autophagy in Heart Failure by Regulating lncRNA TUG1/miR-129-5p/ATG7 Axis [J],” Faseb Journal 37, no. 6 (2023): e22937.

[212] J. Yanni, A. D'Souza, Y. Wang, et al., “Silencing miR-370-3p Rescues Funny Current and Sinus Node Function in Heart Failure [J],” Scientific Reports 10, no. 1 (2020): 11279.

[213] H. Q. Sang, Z. M. Jiang, Q. P. Zhao, et al., “MicroRNA-133a Improves the Cardiac Function and Fibrosis Through Inhibiting Akt in Heart Failure Rats [J],” Biomedicine & Pharmacotherapy 71 (2015): 185–189.

[214] Y. Wang, Y. Yang, T. Zhang, et al., “LncRNA SNHG16 Accelerates Atherosclerosis and Promotes Ox-LDL-induced VSMC Growth via the miRNA-22-3p/HMGB2 Axis [J],” European Journal of Pharmacology 915 (2022): 174601.

[215] J. Wang, L. Zhang, T. Wang, et al., “miRNA-576 Alleviates the Malignant Progression of Atherosclerosis Through Downregulating KLF5 [J],” Disease Markers 2021 (2021): 5450685.

[216] Y. Zhang, Y. Wang, L. Zhang, et al., “Reduced Platelet miR-223 Induction in Kawasaki Disease Leads to Severe Coronary Artery Pathology through a miR-223/PDGFRβ Vascular Smooth Muscle Cell Axis [J],” Circulation Research 127, no. 7 (2020): 855–873.

[217] J. Xiao, Y. Zhang, Y. Tang, et al., “MiRNA-1202 Promotes the TGF-β1-induced Proliferation, Differentiation and Collagen Production of Cardiac Fibroblasts by Targeting nNOS [J],” PLoS ONE 16, no. 8 (2021): e0256066.

[218] G. You, X. Chen, X. Ma, et al., “TAT and RVG Co-modified MSC-derived Exosomes-mediated Delivery of microRNA-15b-5p Inhibitor Alleviate Cerebral Ischemia and Reperfusion-induced Neuronal Apoptosis by Promoting HTR2C-ERK Signaling [J],” Molecular Neurobiology 62, no. 12 (2025): 15813–15831.

[219] M. Le Fur, A. Ross, P. Pantazopoulos, et al., “Radiolabeling and PET-MRI Microdosing of the Experimental Cancer Therapeutic, MN-anti-miR10b, Demonstrates Delivery to Metastatic Lesions in a Murine Model of Metastatic Breast Cancer [J],” Cancer Nanotechnology 12, no. 1 (2021): 16.

[220] J. Rong, T. Liu, X. Yin, et al., “Co-delivery of Camptothecin and MiR-145 by Lipid Nanoparticles for MRI-visible Targeted Therapy of Hepatocellular Carcinoma [J],” Journal of Experimental & Clinical Cancer Research 43, no. 1 (2024): 247.

[221] J. Song, Y. Hu, H. Li, et al., “miR-1303 Regulates BBB Permeability and Promotes CNS Lesions Following CA16 Infections by Directly Targeting MMP9 [J],” Emerging Microbes & Infections 7, no. 1 (2018): 155.

[222] M. Mahjoor, H. Afkhami, M. Mollaei, et al., “MicroRNA-30c Delivered by Bone Marrow-mesenchymal Stem Cells Induced Apoptosis and Diminished Cell Invasion in U-251 Glioblastoma Cell Line [J],” Life Sciences 279 (2021): 119643.

[223] Z. Naseri, R. K. Oskuee, M. R. Jaafari, et al., “Exosome-mediated Delivery of Functionally Active miRNA-142-3p Inhibitor Reduces Tumorigenicity of Breast Cancer in Vitro and in Vivo [J],” International Journal of Nanomedicine 13 (2018): 7727–7747.

[224] K. Wu, J. Feng, F. Lyu, et al., “Exosomal miR-19a and IBSP Cooperate to Induce Osteolytic Bone Metastasis of Estrogen Receptor-positive Breast Cancer [J],” Nature Communications 12, no. 1 (2021): 5196.

[225] S. G. Iyer, I. S. Sohal, and A. L. Kasinski, “Redesigning miR-34a: Structural and Chemical Advances in the Therapeutic Development of an miRNA Anti-cancer Agent [J],” Biochemical Society Transactions (2025): BST20253010.

[226] M. Durso, M. Gaglione, L. Piras, et al., “Chemical Modifications in the Seed Region of miRNAs 221/222 Increase the Silencing Performances in Gastrointestinal Stromal Tumor Cells [J],” European Journal of Medicinal Chemistry 111 (2016): 15–25.

[227] L. Peretz, E. Besser, R. Hajbi, et al., “Combined shRNA Over CRISPR/cas9 as a Methodology to Detect off-target Effects and a Potential Compensatory Mechanism [J],” Scientific Reports 8, no. 1 (2018): 93.

[228] A. Bertero, M. Pawlowski, D. Ortmann, et al., “Optimized Inducible shRNA and CRISPR/Cas9 Platforms for in Vitro Studies of human Development Using hPSCs [J],” Development (Cambridge, England) 143, no. 23 (2016): 4405–4418.

[229] R. M. Deans, D. W. Morgens, A. Ökesli, et al., “Parallel shRNA and CRISPR-Cas9 Screens Enable Antiviral Drug Target Identification [J],” Nature Chemical Biology 12, no. 5 (2016): 361–366.

[230] J. K. Nair, J. L. Willoughby, A. Chan, et al., “Multivalent N-acetylgalactosamine-conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-mediated Gene Silencing [J],” Journal of the American Chemical Society 136, no. 49 (2014): 16958–16961.

[231] J. Hu, X. Gong, J. Kundu, et al., “Modulation of TTR Gene Expression in the Eye Using Modified siRNAs [J],” Nucleic Acids Research 53, no. 9 (2025): gkaf409.

[232] W. Ji, Y. Li, H. Peng, et al., “Self-Catalytic Small Interfering RNA Nanocarriers for Synergistic Treatment of Neurodegenerative Diseases [J],” Advanced Materials 34, no. 1 (2022): e2105711.

[233] L. J. Mao, J. Zhang, N. Liu, et al., “Oncolytic Virus Carrying shRNA Targeting SATB1 Inhibits Prostate Cancer Growth and Metastasis [J],” Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 36, no. 11 (2015): 9073–9081.

[234] A. Sharma, P. McCarron, K. Matchett, et al., “Anti-Invasive and Anti-Proliferative Effects of shRNA-Loaded Poly(Lactide-Co-Glycolide) Nanoparticles Following RAN Silencing in MDA-MB231 Breast Cancer Cells [J],” Pharmaceutical Research 36, no. 2 (2018): 26.

[235] N. Allahyarzadeh Khiabani, M. Amin Doustvandi, F. Mohammadnejad, et al., “Combination of B7H6-siRNA and Temozolomide Synergistically Reduces Stemness and Migration Properties of Glioblastoma Cancer Cells [J],” Experimental Cell Research 429, no. 1 (2023): 113667.

[236] L. L. Wang, J. J. Chung, E. C. Li, et al., “Injectable and Protease-degradable Hydrogel for siRNA Sequestration and Triggered Delivery to the Heart [J],” Journal of Controlled Release 285 (2018): 152–161.

[237] E. Amjadimanesh, A. Mokhtari, and B. Saffar, “RNA Interference Targeting UL25 Gene as a Gene Therapy Approach Against BHV-1 [J],” Research in Veterinary Science 145 (2022): 109–115.

[238] D. Wen, H. Xiao, Y. Gao, et al., “N6-methyladenosine-modified SENP1, Identified by IGF2BP3, Is a Novel Molecular Marker in Acute Myeloid Leukemia and Aggravates Progression by Activating AKT Signal via De-SUMOylating HDAC2 [J],” Molecular Cancer 23, no. 1 (2024): 116.

[239] Y. Xia, C. He, Z. Hu, et al., “The Mitochondrial Protein YME1 Like 1 Is Important for Non-small Cell Lung Cancer Cell Growth [J],” International Journal of Biological Sciences 19, no. 6 (2023): 1778.

[240] L. Liu, X. Chen, K. Huang, et al., Ubiquitin Ligase Subunit FBXO9 Inhibits V-ATPase Assembly and Lung Cancer Metastasis [Z] (American Society of Clinical Oncology, 2024).

[241] E. Bayraktar, C. Rodriguez-Aguayo, E. Stur, et al., “Epigenetic Modulation of BARD1 to Enhance Anti-VEGF Therapy [J],” Cell Reports Medicine 6, no. 9 (2025): 102329.

[242] Y.-H. Sang, C.-Y. Luo, B.-T. Huang, et al., “Elevated Origin Recognition Complex Subunit 6 Expression Promotes Non-small Cell Lung Cancer Cell Growth [J],” Cell Death & Disease 15, no. 9 (2024): 700.

[243] W.-L. Yang, W.-F. Zhang, Y. Wang, et al., “Origin Recognition Complex 6 Overexpression Promotes Growth of Glioma Cells [J],” Cell Death & Disease 15, no. 7 (2024): 485.

[244] D.-P. Yin, H. Zhang, H. Teng, et al., “Overexpressed Gαi1 Exerts Pro-tumorigenic Activity in Nasopharyngeal Carcinoma [J],” Cell Death & Disease 14, no. 12 (2023): 792.

[245] Y. Zhou, T. Lei, Z. Tang, et al., “Increased Phosphorylation of AMPKα1 S485 in Colorectal Cancer and Identification of PKCα as a Responsible Kinase [J],” Cancer Letters 611 (2025): 217418.

[246] M. Li, L. Chen, M. Wang, et al., “Curcumin Alleviates the Aggressiveness of Breast Cancer Through Inhibiting Cell Adhesion Mediated by TEAD4-fibronectin Axis [J],” Biochemical Pharmacology 232 (2025): 116690.

[247] W. Xu, H. Fang, X. Cao, et al., “NADH: Ubiquinone Oxidoreductase Core Subunit S8 Expression and Functional Significance in Non-small Cell Lung Cancer [J],” Cell Death & Disease 16, no. 1 (2025): 321.

[248] Y. Liu, A. Chen, Y. Wu, et al., “Identification of Mitochondrial Carrier Homolog 2 as an Important Therapeutic Target of Castration-resistant Prostate Cancer [J],” Cell Death & Disease 16, no. 1 (2025): 70.

[249] L. R. Velatooru, C. H. Hu, P. Bijani, et al., “New JAK3-INSL3 Fusion Transcript—an Oncogenic Event in Cutaneous T-cell Lymphoma [J],” Cells 12, no. 19 (2023): 2381.

[250] Y. Wang, F. Liu, J. Wu, et al., “G Protein Inhibitory α Subunit 2 Is a Molecular Oncotarget of human Glioma [J],” International Journal of Biological Sciences 19, no. 3 (2023): 865.

[251] S.-L. Ming, S. Zhang, Q. Wang, et al., “Inhibition of USP14 Influences Alphaherpesvirus Proliferation by Degrading Viral VP16 Protein via ER Stress-triggered Selective Autophagy [J],” Autophagy 18, no. 8 (2022): 1801–1821.

[252] P. Hou, X. Wang, H. Wang, et al., “The ORF7a Protein of SARS-CoV-2 Initiates Autophagy and Limits Autophagosome-lysosome Fusion via Degradation of SNAP29 to Promote Virus Replication [J],” Autophagy 19, no. 2 (2023): 551–569.

[253] S. F. Pedersen, J. A. Collora, R. N. Kim, et al., “Inhibition of a Chromatin and Transcription Modulator, SLTM, Increases HIV-1 Reactivation Identified by a CRISPR Inhibition Screen [J],” Journal of Virology 96 no. 13 (2022): e00577–e00582.

[254] W. Jin, J. Zhao, E. Yang, et al., “Neuronal STAT3/HIF-1α/PTRF Axis-mediated Bioenergetic Disturbance Exacerbates Cerebral Ischemia-reperfusion Injury via PLA2G4A [J],” Theranostics 12, no. 7 (2022): 3196.

[255] J. Tuma, Y.-J. Chen, M. G. Collins, et al., “Lipid Nanoparticles Deliver mRNA to the Brain After an Intracerebral Injection [J],” Biochemistry 62, no. 24 (2023): 3533–3547.

[256] Z. Chu, Y. Zheng, Q. Shen, et al., “Neutrophil Extracellular Traps With Low Concentrations Induce Proliferation and Migration of human Fibroblasts via Activating CCDC25/ILK/PI3K/AKT Pathway [J],” Biochemical and Biophysical Research Communications 738 (2024): 150954.

[257] Z. Yan, J. Zhu, Y. Liu, et al., “DNA-PKcs/AKT1 Inhibits Epithelial–mesenchymal Transition During Radiation-induced Pulmonary Fibrosis by Inducing Ubiquitination and Degradation of Twist1 [J],” Clinical and Translational Medicine 14, no. 5 (2024): e1690.

[258] Z.-R. Ma, H.-P. Li, S.-Z. Cai, et al., “The Mitochondrial Protein TIMM44 Is Required for Angiogenesis in Vitro and in Vivo [J],” Cell Death & Disease 14, no. 5 (2023): 307.

[259] J. Li, C. Chen, C. Li, et al., “Genome-wide Knockout Screen Identifies EGLN3 Involving in Ammonia Neurotoxicity [J],” Frontiers in Cell and Developmental Biology 10 (2022): 820692.

[260] S. Ambike, C.-C. Cheng, M. Feuerherd, et al., “Targeting Genomic SARS-CoV-2 RNA With siRNAs Allows Efficient Inhibition of Viral Replication and Spread [J],” Nucleic Acids Research 50, no. 1 (2022): 333–349.

[261] D. Shaliman, H. Takenobu, R. P. Sugino, et al., “The PRC2 Molecule EED Is a Target of Epigenetic Therapy for Neuroblastoma [J],” European Journal of Cell Biology 101, no. 3 (2022): 151238.

[262] M. Chen, Z. Li, C. Gu, et al., “Identification of G Protein Subunit Alpha i2 as a Promising Therapeutic Target of Hepatocellular Carcinoma [J],” Cell Death & Disease 14, no. 2 (2023): 143.

[263] P. Carpintero-Fernández, M. Borghesan, O. Eleftheriadou, et al., “Genome Wide CRISPR/Cas9 Screen Identifies the Coagulation Factor IX (F9) as a Regulator of Senescence [J],” Cell Death & Disease 13, no. 2 (2022): 163.

[264] X. Jin, S. Yang, X. Lu, et al., “Increased Expression of REG3A Promotes Tumorigenic Behavior in Triple Negative Breast Cancer Cells [J],” Breast Cancer Research 26, no. 1 (2024): 92.

[265] M. Yang, Q. Li, H. Yang, et al., “Downregulation of PDIA3 Inhibits Gastric Cancer Cell Growth Through Cell Cycle Regulation [J],” Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 173 (2024): 116336.

[266] J. S. Kim, J. H. Lee, S.-R. Jeon, et al., “Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers [J],” Cancer Research and Treatment: Official Journal of Korean Cancer Association 55, no. 3 (2023): 737–756.

[267] D. Liu, J. Du, H. Xie, et al., “Wnt5a/β-catenin-mediated Epithelial-mesenchymal Transition: A Key Driver of Subretinal Fibrosis in Neovascular Age-related Macular Degeneration [J],” Journal of Neuroinflammation 21, no. 1 (2024): 75.

[268] E. Slaman, M. Lammers, G. C. Angenent, et al., “High-throughput sgRNA Testing Reveals Rules for Cas9 Specificity and DNA Repair in Tomato Cells [J],” Frontiers in Genome Editing 5 (2023): 1196763.

[269] G. Zhang, T. Zeng, Z. Dai, et al., “Prediction of CRISPR/Cas9 Single Guide RNA Cleavage Efficiency and Specificity by Attention-based Convolutional Neural Networks [J],” Computational and Structural Biotechnology Journal 19 (2021): 1445–1457.

[270] J. K. Dhanjal, S. Dammalapati, S. Pal, et al., “Evaluation of off-targets Predicted by sgRNA Design Tools [J],” Genomics 112, no. 5 (2020): 3609–3614.

[271] M. Schaefer, D. A. Clevert, B. Weiss, et al., “PAVOOC: Designing CRISPR sgRNAs Using 3D Protein Structures and Functional Domain Annotations [J],” Bioinformatics 35, no. 13 (2019): 2309–2310.

[272] W. Du, L. Zhao, K. Diao, et al., “A Versatile CRISPR/Cas9 System off-target Prediction Tool Using Language Model [J],” Communications Biology 8, no. 1 (2025): 882.

[273] Q. Liu, D. He, and L. Xie, “Prediction of off-target Specificity and Cell-specific Fitness of CRISPR-Cas System Using Attention Boosted Deep Learning and Network-based Gene Feature [J],” Plos Computational Biology 15, no. 10 (2019): e1007480.

[274] K. D. Kiran Kumar, S. Singh, S. M. Schmelzle, et al., “An Improved SNAP-ADAR Tool Enables Efficient RNA Base Editing to Interfere With Post-translational Protein Modification [J],” Nature Communications 15, no. 1 (2024): 6615.

[275] J. Chen, Y. Xu, M. Zhou, et al., “Combinatorial Design of Ionizable Lipid Nanoparticles for Muscle-selective mRNA Delivery With Minimized off-target Effects [J],” Proceedings of the National Academy of Sciences of the United States of America 120, no. 50 (2023): e2309472120.

[276] A. Weiss, J. W. Gilbert, I. V. R. Flores, et al., “RNAi-mediated Silencing of SOD1 Profoundly Extends Survival and Functional Outcomes in ALS Mice [J],” Molecular Therapy 33, no. 8 (2025): 3917–3938.

[277] W. Ren, Y. Chi, and J. Sun, “Effect of shRNA-mediated Regulation of S100A4 Gene Expression on Proliferation and Apoptosis of KLE Endometrial Cancer Cells [J],” Clinical and Translational Oncology 23, no. 1 (2021): 148–154.

[278] Z. Zhang, F. Liu, Y. Yu, et al., “Prognosis and Immune Landscape of Bladder Cancer Can be Predicted Using a Novel miRNA Signature Associated With Cuproptosis [J],” PeerJ 12 (2024): e18530.

[279] E. S. Stroes, V. J. Alexander, E. Karwatowska-Prokopczuk, et al., “Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome [J],” New England Journal of Medicine 390, no. 19 (2024): 1781–1792.

[280] S. E. Nissen, Q. Wang, S. J. Nicholls, et al., “Zerlasiran—a Small-interfering RNA Targeting Lipoprotein (a): A Phase 2 Randomized Clinical Trial [J],” Jama 332, no. 23 (2024): 1992–2002.

[281] J. S. Weber, M. S. Carlino, A. Khattak, et al., “Individualised Neoantigen Therapy mRNA-4157 (V940) plus Pembrolizumab versus Pembrolizumab Monotherapy in Resected Melanoma (KEYNOTE-942): A Randomised, Phase 2b Study [J],” The Lancet 403, no. 10427 (2024): 632–644.

[282] D. Adams, A. Gonzalez-Duarte, W. D. O'Riordan, et al., “Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis [J],” New England Journal of Medicine 379, no. 1 (2018): 11–21.

[283] M. S. Maurer, P. Kale, M. Fontana, et al., “Patisiran Treatment in Patients With Transthyretin Cardiac Amyloidosis [J],” New England Journal of Medicine 389, no. 17 (2023): 1553–1565.

[284] K. K. Ray, R. S. Wright, D. Kallend, et al., “Two Phase 3 Trials of inclisiran in Patients With Elevated LDL Cholesterol [J],” New England Journal of Medicine 382, no. 16 (2020): 1507–1519.

[285] R. S. Wright, K. K. Ray, F. J. Raal, et al., “Pooled Patient-level Analysis of inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis [J],” Journal of the American College of Cardiology 77, no. 9 (2021): 1182–1193.

[286] G. Acsadi, T. O. Crawford, W. Müller-Felber, et al., “Safety and Efficacy of nusinersen in Spinal Muscular Atrophy: The EMBRACE Study [J],” Muscle & Nerve 63, no. 5 (2021): 668–677.

[287] C. M. Proud, R. S. Finkel, J. A. Parsons, et al., “Open-label Phase 4 Trial Evaluating nusinersen After onasemnogene abeparvovec in Children With Spinal Muscular Atrophy [J],” The Journal of Clinical Investigation 135, no. 22 (2025): e193956.

[288] K. A. Strauss, M. A. Farrar, F. Muntoni, et al., “Onasemnogene abeparvovec for Presymptomatic Infants With Three Copies of SMN2 at Risk for Spinal Muscular Atrophy: The Phase III SPR1NT Trial [J],” Nature Medicine 28, no. 7 (2022): 1390–1397.

[289] J. W. Day, R. S. Finkel, C. A. Chiriboga, et al., “Onasemnogene abeparvovec Gene Therapy for Symptomatic Infantile-onset Spinal Muscular Atrophy in Patients With Two Copies of SMN2 (STR1VE): An Open-label, Single-arm, Multicentre, Phase 3 Trial [J],” The Lancet Neurology 20, no. 4 (2021): 284–293.

[290] M. Balwani, E. Sardh, P. Ventura, et al., “Phase 3 Trial of RNAi Therapeutic givosiran for Acute Intermittent Porphyria [J],” New England Journal of Medicine 382, no. 24 (2020): 2289–2301.

[291] D. J. Kuter, H. L. Bonkovsky, S. Monroy, et al., “Efficacy and Safety of givosiran for Acute Hepatic Porphyria: Final Results of the Randomized Phase III ENVISION Trial [J],” Journal of Hepatology 79, no. 5 (2023): 1150–1158.

[292] A. Poli, C. Schmitt, B. Moulouel, et al., “Givosiran in Acute Intermittent Porphyria: A Personalized Medicine Approach [J],” Molecular Genetics and Metabolism 135, no. 3 (2022): 206–214.

[293] P. Ventura, H. L. Bonkovsky, L. Gouya, et al., “Efficacy and Safety of givosiran for Acute Hepatic Porphyria: 24-month Interim Analysis of the Randomized Phase 3 ENVISION Study [J],” Liver International 42, no. 1 (2022): 161–172.

[294] M. Michael, J. W. Groothoff, H. Shasha-Lavsky, et al., “Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial [J],” American Journal of Kidney Diseases 81, no. 2 (2023): 145–155.e1.

[295] F. Taroni, L. Peruzzi, G. Longo, et al., “Lumasiran Treatment in Pediatric Patients With PH1: Real-world Data Within a Compassionate Use Program in Italy [J],” Clinical Kidney Journal 17, no. 5 (2024): sfae090.

[296] Y. Frishberg, W. Hayes, H. Shasha-Lavsky, et al., “Efficacy and Safety of lumasiran for Infants and Young Children With Primary Hyperoxaluria Type 1: 30-month Analysis of the Phase 3 ILLUMINATE-B Trial [J],” Frontiers in Pediatrics 12 (2024): 1392644.

[297] I. Gouni-Berthold, V. J. Alexander, Q. Yang, et al., “Efficacy and Safety of volanesorsen in Patients With Multifactorial Chylomicronaemia (COMPASS): A Multicentre, Double-blind, Randomised, Placebo-controlled, Phase 3 Trial [J],” The Lancet Diabetes & Endocrinology 9, no. 5 (2021): 264–275.

[298] G. Young, A. Srivastava, K. Kavakli, et al., “Efficacy and Safety of fitusiran Prophylaxis in People With Haemophilia A or Haemophilia B With Inhibitors (ATLAS-INH): A Multicentre, Open-label, Randomised Phase 3 Trial [J],” The Lancet 401, no. 10386 (2023): 1427–1437.

[299] B. Van De Sande, J. S. Lee, E. Mutasa-Gottgens, et al., “Applications of Single-cell RNA Sequencing in Drug Discovery and Development [J],” Nature Reviews Drug Discovery 22, no. 6 (2023): 496–520.

[300] X. Li, J. Li, J. Wei, et al., “Design Strategies for Novel Lipid Nanoparticle for mRNA Vaccine and Therapeutics: Current Understandings and Future Perspectives [J],” MedComm 6, no. 10 (2025): e70414.

[301] J. Sikorska, Y. Hou, P. Chiurazzi, et al., “Characterization of RNA Driven Structural Changes in Full Length RIG-I Leading to Its Agonism or Antagonism [J],” Nucleic Acids Research 51, no. 17 (2023): 9356–9368.

[302] E. Oude Blenke, E. Örnskov, C. Schöneich, et al., “The Storage and in-use Stability of mRNA Vaccines and Therapeutics: Not a Cold Case [J],” Journal of Pharmaceutical Sciences 112, no. 2 (2023): 386–403.

[303] J. Y. Park, Y. L. Cho, J. R. Chae, et al., “Enhancement of in Vivo Targeting Properties of ErbB2 Aptamer by Chemical Modification [J],” PLoS ONE 18, no. 9 (2023): e0291624.

[304] G. Kumar and A. M. Ardekani, “Machine-Learning Framework to Predict the Performance of Lipid Nanoparticles for Nucleic Acid Delivery [J],” ACS Applied Bio Materials 8, no. 5 (2025): 3717–3727.

[305] H. Yu, H. Yang, W. Sun, et al., “An Interpretable RNA Foundation Model for Exploring Functional RNA Motifs in Plants [J],” Nature Machine Intelligence 6, no. 12 (2024): 1616–1625.

[306] Y. Fei, X. Yu, P. Liu, et al., “Simplified Lipid Nanoparticles for Tissue-And Cell-Targeted mRNA Delivery Facilitate Precision Tumor Therapy in a Lung Metastasis Mouse Model [J],” Advanced Materials 36, no. 48 (2024): 2409812.

[307] Y. L. Wu, S. Lu, Q. Zhou, et al., “Expert Consensus on Treatment for Stage III Non-small Cell Lung Cancer [J],” Medicine Advances 1, no. 1 (2023): 3–13.

[308] W. Zhou, X. Liu, Z. Li, et al., “Epigenetic Crosstalk Between Stem Cells and Tumors: Mechanisms and Emerging Perspectives [J],” American Journal of Stem Cells 14, no. 3 (2025): 98.

[309] J. M. Li, J. Huang, Y. Liao, et al., “Gene and RNA Editing: Revolutionary Approaches to Treating Diseases [J],” MedComm 6, no. 10 (2025): e70389.

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