Gene silencing by RNA interference: a review

Suresh Malakondaiah , Angeline Julius , Divyadharshini Ponnambalam , Summana Sree Gunthoti , Joshitha Ashok , Poorni Santhana Krishana , Jeyanthi Rebecca

Genome Instability & Disease ›› 2024, Vol. 5 ›› Issue (5) : 225 -241.

PDF
Genome Instability & Disease ›› 2024, Vol. 5 ›› Issue (5) : 225 -241. DOI: 10.1007/s42764-024-00135-7
Review Article

Gene silencing by RNA interference: a review

Author information +
History +
PDF

Abstract

RNA interference (RNAi)-based gene silencing has emerged as a potent method for regulating gene expression, with applications spanning biology, medicine, and biotechnology. RNAi exploits natural cellular machinery to selectively suppress target gene expression through the targeted degradation of mRNA based on its specific sequence. MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are two examples of tiny RNA molecules that are introduced during this process; they direct the silencing complex induced by RNA (RISC) in response to complementary mRNA and repress its translation. Several biological functions, including cellular homeostasis maintenance and developmental regulation against viral infections and transposable elements, depend heavily on RNAi-mediated gene silencing. In research, RNAi has revolutionized functional genomics by enabling high-throughput analysis of gene functions and regulatory networks. Moreover, RNAi-based screening approaches have facilitated the discovery of novel drug targets and therapeutic agents. In medicine, RNAi shows potential for addressing genetic disorders, viral infections, cancer, and other diseases by providing a means for precise and targeted intervention. Nevertheless, issues with delivery, specificity, immunogenicity, and safety impede the clinical translation of RNAi-based treatments. RNAi has shown great promise in biotechnology and agriculture for bioproduction, crop improvement, and pest management. Despite these challenges, the rapid advancement of RNAi research and technology holds immense potential to further our understanding of gene regulation and revolutionize therapeutic interventions. An overview of the relevance and uses of RNAi in gene silencing is given in this review, emphasizing the role it will play in directing future biological and medical research.

Cite this article

Download citation ▾
Suresh Malakondaiah, Angeline Julius, Divyadharshini Ponnambalam, Summana Sree Gunthoti, Joshitha Ashok, Poorni Santhana Krishana, Jeyanthi Rebecca. Gene silencing by RNA interference: a review. Genome Instability & Disease, 2024, 5(5): 225-241 DOI:10.1007/s42764-024-00135-7

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

AbosalhaAK, BoyajianJ, AhmadW, IslamP, GhebretatiosM, SchalyS, TharejaR, AroraK, PrakashS. Clinical pharmacology of siRNA therapeutics: Current status and future prospects. Expert Review of Clinical Pharmacology, 2022, 15(11): 1327-1341

[2]

Ashraf, S., Ghouri, M. Z., Javed, M. A., Zafar, H., Ali, H., Qari, S. H., & Ahmad, A. (2022). Rna Editing with Crispr/Cas13. The CRISPR/Cas Tool Kit for Genome Editing, 219–254.

[3]

AsohanJ, FakihHH, DasT, SleimanHF. Control of the Assembly and Disassembly of spherical nucleic acids is critical for enhanced gene silencing. Acs Nano, 2024, 18(5): 3996-4007

[4]

BabuA, MuralidharanR, AmreddyN, MehtaM, MunshiA, RameshR. Nanoparticles for siRNA-based gene silencing in tumor therapy. IEEE Transactions on Nanobioscience, 2016, 15(8): 849-863

[5]

BakrisGL, SaxenaM, GuptaA, ChalhoubF, LeeJ, StiglitzD, MakarovaN, GoyalN, GuoW, ZappeD. RNA interference with zilebesiran for mild to moderate hypertension: The KARDIA-1 Randomized Clinical Trial. Journal of the American Medical Association, 2024, 331(9): 740-749

[6]

BeginesB, OrtizT, Pérez-ArandaM, MartínezG, MerineroM, Argüelles-AriasF, AlcudiaA. Polymeric nanoparticles for drug delivery: Recent developments and future prospects. Nanomaterials, 2020, 10(7): 1403

[7]

BerbatiM, KaldisA, VoloudakisA. Efficient artificial microRNA-mediated resistance against zucchini yellow mosaic virus in zucchini via agroinfiltration. Journal of Virological Methods, 2023, 321: 114805

[8]

BlomDJ, MaraisAD, MoodleyR, van der MerweN, van TonderA, RaalFJ. RNA-based therapy in the management of lipid disorders: A review. Lipids in Health and Disease, 2022, 21(1): 41

[9]

Bonfante, P., Nuti, M., & Stocchi, V. (2012). Biotechnology of Ectomycorrhizae: Molecular approaches. Springer Science & Business Media.

[10]

Chardon, F. (2023). CRISPR-Based Functional Genomics to Study Gene Regulatory Architecture and consequences of genetic variation. University of Washington.

[11]

ChenJ, PengY, ZhangH, WangK, ZhaoC, ZhuG, PalliR, HanZ. Off-target effects of RNAi correlate with the mismatch rate between dsRNA and non-target mRNA. RNA Biology, 2021, 18(11): 1747-1759

[12]

Choudry, M. W., Nawaz, P., Jahan, N., Riaz, R., Ahmad, B., Raza, M. H., Fayaz, Z., Malik, K., & Afzal, S. (2024). RNA based gene silencing modalities to control insect and fungal plant pests–challenges and future prospects. Physiological and Molecular Plant Pathology, 102241.

[13]

CisnerosAE, Martín-GarcíaT, PrimcA, KuziutaW, Sánchez-VicenteJ, AragonésV, DaròsJA, CarbonellA. Transgene-free, virus-based gene silencing in plants by artificial microRNAs derived from minimal precursors. Nucleic Acids Research, 2023, 51(19): 10719-10736

[14]

CohenS, DucharmeS, BroschJR, VijverbergEGB, ApostolovaLG, SostellyA, GotetiS, MakarovaN, AvbersekA, GuoW. Interim phase 1 part A results for ALN-APP, the first investigational RNAi therapeutic in development for Alzheimer’s disease. Alzheimer’s & Dementia, 2023, 19: e082650

[15]

CuiL, MaR, CaiJ, GuoC, ChenZ, YaoL, WangY, FanR, WangX, ShiY. RNA modifications: Importance in immune cell biology and related diseases. Signal Transduction and Targeted Therapy, 2022, 7(1): 334

[16]

Cummings, J. (2019). The role of biomarkers in Alzheimer’s disease drug development. Reviews on Biomarker Studies in Psychiatric and Neurodegenerative Disorders, 29–61.

[17]

De FelippesFF, WaterhousePM. Plant terminators: The unsung heroes of gene expression. Journal of Experimental Botany, 2023, 74(7): 2239-2250

[18]

DingSW. Transgene silencing, RNA interference, and the antiviral defense mechanism directed by small interfering RNAs. Phytopathology®, 2023, 113(4): 616-625

[19]

DongZ, PengJ, GuoS. Stable gene silencing in zebrafish with spatiotemporally targetable RNA interference. Genetics, 2013, 193(4): 1065-1071

[20]

El-SappahAH, YanK, HuangQ, IslamMM, LiQ, WangY, KhanMS, ZhaoX, MirRR, LiJ. Comprehensive mechanism of gene silencing and its role in plant growth and development. Frontiers in Plant Science, 2021, 12: 705249

[21]

GaetaAL, Nourse JrJB, WillicottK, McKayLE, KeoghCM, PeterK, RussellSN, HamamichiS, BerkowitzLA, CaldwellKA. Systemic RNA interference defective (SID) genes modulate dopaminergic neurodegeneration in C. Elegans. PloS Genetics, 2022, 18(8): e1010115

[22]

Gao, J., & Li, F. (2024). Heterochromatin repeat organization at an individual level: Rex1BD and the 14-3‐3 protein coordinate to shape the epigenetic landscape within heterochromatin repeats. Bioessays, 2400030.

[23]

GebremichaelDE, HaileZM, NegriniF, SabbadiniS, CapriottiL, MezzettiB, BaraldiE. RNA interference strategies for future management of plant pathogenic fungi: Prospects and challenges. Plants, 2021, 10(4): 650

[24]

GomaseVS, TagoreS. RNAi-a tool for target finding in new drug development. Current Drug Metabolism, 2008, 9(3): 241-244

[25]

HarrisGA, HirschfeldLR. Antisense oligonucleotides provide optimism to the therapeutic landscape for tauopathies. Neural Regeneration Research, 2025, 20(3): 803-804

[26]

HorvathovaI, VoigtF, KotrysAV, ZhanY, Artus-RevelCG, EglingerJ, StadlerMB, GiorgettiL, ChaoJA. The dynamics of mRNA turnover revealed by single-molecule imaging in single cells. Molecular Cell, 2017, 68(3): 615-625

[27]

HungYH, SlotkinRK. The initiation of RNA interference (RNAi) in plants. Current Opinion in Plant Biology, 2021, 61: 102014

[28]

HussainSS, AbbasM, AbbasS, WeiM, El-SappahAH, SunY, LiY, RagauskasAJ, LiQ. Alternative splicing: Transcriptional regulatory network in agroforestry. Frontiers in Plant Science, 2023, 14: 1158965

[29]

HutsonTH, FosterE, MoonLDF, Yánez-MunozRJ. Lentiviral vector-mediated RNA silencing in the central nervous system. Human Gene Therapy Methods, 2014, 25(1): 14-32

[30]

Jones, H. D. (2021). Gene silencing or gene editing: The pros and cons. RNAi for plant improvement and protection (pp. 47–53). CABI Wallingford UK.

[31]

KangH, GaYJ, KimSH, ChoYH, KimJW, KimC, YehJY. Small interfering RNA (siRNA)-based therapeutic applications against viruses: Principles, potential, and challenges. Journal of Biomedical Science, 2023, 30(1): 88

[32]

KochA, WasseneggerM. Host-induced gene silencing–mechanisms and applications. New Phytologist, 2021, 231(1): 54-59

[33]

KoeppeS, KawchukL, KalischukM. RNA interference past and future applications in plants. International Journal of Molecular Sciences, 2023, 24(11): 9755

[34]

Koh, H. B., Kim, H. J., Kang, S. W., & Yoo, T. H. (2023). Exosome-based drug delivery: translation from bench to clinic. Pharmaceutics, 15(8), 2042.

[35]

LiY, FangH, ZhangT, WangY, QiT, LiB, JiaoH. Lipid-mRNA nanoparticles landscape for cancer therapy. Frontiers in Bioengineering and Biotechnology, 2022, 10: 1053197

[36]

LiG, MichaelisDF, HuangJ, SerekM, GehlC. New insights into the genetic manipulation of the R2R3-MYB and CHI gene families on anthocyanin pigmentation in Petunia hybrida. Plant Physiology and Biochemistry, 2023, 203: 108000

[37]

LiuX, JinDY, McManusMT, MourelatosZ. Precursor microRNA-programmed silencing complex assembly pathways in mammals. Molecular Cell, 2012, 46(4): 507-517

[38]

Liu, S., Geng, S., Li, A., Mao, Y., & Mao, L. (2021). RNAi technology for plant protection and its application in wheat. Abiotech, 1–10.

[39]

Loscalzo, J., & Handy, D. E. (2014). Epigenetic modifications: basic mechanisms and role in cardiovascular disease (2013 Grover Conference series). Pulmonary Circulation, 4(2), 169–174.

[40]

Lu, A. T., Fei, Z., Haghani, A., Robeck, T. R., Zoller, J. A., Li, C. Z., Lowe, R., Yan, Q., Zhang, J., & Vu, H. (2021). Universal DNA methylation age across mammalian tissues. BioRxiv, 2001–2021.

[41]

MargusH, PadariK, PoogaM. Cell-penetrating peptides as versatile vehicles for oligonucleotide delivery. Molecular Therapy, 2012, 20(3): 525-533

[42]

Millán-ZambranoG, BurtonA, BannisterAJ, SchneiderR. Histone post-translational modifications—cause and consequence of genome function. Nature Reviews Genetics, 2022, 23(9): 563-580

[43]

NapoliC, LemieuxC, JorgensenR. Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous genes in trans. The Plant Cell, 1990, 2(4): 279-289

[44]

NiaziSK. The Dawn of in vivo gene editing era: A Revolution in the making. Biologics, 2023, 3(4): 253-295

[45]

NiuJ, ChenR, WangJ. RNA interference in insects: The link between antiviral defense and pest control. Insect Science, 2024, 31(1): 2-12

[46]

O’BrienJ, HayderH, ZayedY, PengC. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Frontiers in Endocrinology, 2018, 9: 402

[47]

OrtoláB, DaròsJA. RNA interference in insects: From a natural mechanism of gene expression regulation to a biotechnological crop protection promise. Biology, 2024, 13(3): 137

[48]

Pandey, P., Mysore, K. S., & Senthil-Kumar, M. (2022). Recent advances in plant gene silencing methods. Plant Gene Silencing: Methods and Protocols, 1–22.

[49]

Pardridge, W. M. (2022). Advanced blood–brain barrier drug delivery. Pharmaceutics (Vol. 15, p. 93). MDPI. 1.

[50]

ParkM, UmTY, JangG, ChoiY, Do, ShinC. Targeted gene suppression through double-stranded RNA application using easy-to-use methods in Arabidopsis thaliana. Applied Biological Chemistry, 2022, 65(1): 4

[51]

ParveenS, KhanA, JahanN, AaliyaK, MuzaffarA, TabassumB, InayatullahS, MoeezullahS, TariqM, RehmatZ. Expression of chitinase and shRNA gene exhibits resistance to fungi and virus. Genes, 2023, 14(5): 1090

[52]

Pun, F. W., Ozerov, I. V., & Zhavoronkov, A. (2023). AI-powered therapeutic target discovery. Trends in Pharmacological Sciences.

[53]

QuinzoMJ, PerteguerMJ, BrindleyPJ, LoukasA, SotilloJ. Transgenesis in parasitic helminths: A brief history and prospects for the future. Parasites & Vectors, 2022, 15(1): 110

[54]

RabumaT, GuptaOP, ChhokarV. Recent advances and potential applications of cross-kingdom movement of miRNAs in modulating plant’s disease response. RNA Biology, 2022, 19(1): 519-532

[55]

RanasingheP, AddisonML, DearJW, WebbDJ. Small interfering RNA: Discovery, pharmacology and clinical development—An introductory review. British Journal of Pharmacology, 2023, 180(21): 2697-2720

[56]

RedhwanMAM, SamaddarMGH, HardS, YadavSAAA, MukherjeeV, KumarR. Small interference (RNAi) technique: Exploring its clinical applications, benefits and limitations. European Journal of Clinical Investigation, 2023, 53(10): e14039

[57]

Rodríguez MeloJ, MammarellaF, ArielF. Exogenous RNAs: Promising tools for the second green revolution. Journal of Experimental Botany, 2023, 74(7): 2323-2337

[58]

Saakre, M., Jaiswal, S., Rathinam, M., Raman, K. V., Tilgam, J., Paul, K., Sreevathsa, R., & Pattanayak, D. (2023). Host-delivered RNA interference for durable pest resistance in plants: Advanced methods, challenges, and applications. Molecular Biotechnology, 1–20.

[59]

Sarkar, A., Singh, P., & Varkey, M. (2024). Healthcare Artificial Intelligence in India and ethical aspects. AI, consciousness and the New Humanism: Fundamental reflections on minds and machines (pp. 107–150). Springer.

[60]

Sehki, H., Yu, A., Elmayan, T., & Vaucheret, H. (2023). TYMV and TRV infect Arabidopsis thaliana by expressing weak suppressors of RNA silencing and inducing host RNASE THREE LIKE1. PLoS Pathogens, 19(1), e1010482.

[61]

Semple, S. L., Au, S. K., Jacob, R. A., Mossman, K. L., & DeWitte-Orr, S. J. (2022). Discovery and use of long dsRNA mediated RNA interference to stimulate antiviral protection in interferon-competent mammalian cells. Frontiers in Immunology, 13, 859749.

[62]

ShangR, LeeS, SenavirathneG, LaiEC. microRNAs in action: Biogenesis, function and regulation. Nature Reviews Genetics, 2023, 24(12): 816-833

[63]

SinghH, DasA, KhanMM, PourmotabbedT. New insights into the therapeutic approaches for the treatment of tauopathies. Neural Regeneration Research, 2024, 19(5): 1020-1026

[64]

Skotte, N. H., Southwell, A. L., Østergaard, M. E., Carroll, J. B., Warby, S. C., Doty, C. N., Petoukhov, E., Vaid, K., Kordasiewicz, H., & Watt, A. T. (2014). Allele-specific suppression of mutant huntingtin using antisense oligonucleotides: Providing a therapeutic option for all Huntington disease patients. PloS One, 9(9), e107434.

[65]

SledzCA, WilliamsBRG. RNA interference in biology and disease. Blood, 2005, 106(3): 787-794

[66]

SongMS, RossiJJ. Molecular mechanisms of Dicer: Endonuclease and enzymatic activity. Biochemical Journal, 2017, 474(10): 1603-1618

[67]

SvobodaP. Key mechanistic principles and considerations concerning RNA interference. Frontiers in Plant Science, 2020, 11: 1237

[68]

TalianskyME, LoveAJ, Kołowerzo-LubnauA, SmolińskiDJ. Cajal bodies: Evolutionarily conserved nuclear biomolecular condensates with properties unique to plants. The Plant Cell, 2023, 35(9): 3214-3235

[69]

TianZ, LiangG, CuiK, LiangY, WangQ, LvS, ChengX, ZhangL. Insight into the prospects for RNAi therapy of cancer. Frontiers in Pharmacology, 2021, 12: 644718

[70]

Torri, A., Jaeger, J., Pradeu, T., & Saleh, M. C. (2022). The origin of RNA interference: Adaptive or neutral evolution? PLoS Biology, 20(6), e3001715.

[71]

Trasser, M., Bohl-Viallefond, G., Barragan-Borrero, V., Diezma-Navas, L., Loncsek, L., Nordborg, M., & Mari-Ordonez, A. (2024). PTGS is dispensable for the initiation of epigenetic silencing of an active transposon in Arabidopsis. BioRxiv, 2005–2024.

[72]

VarkeyB. Principles of clinical ethics and their application to practice. Medical Principles and Practice, 2021, 30(1): 17-28

[73]

VoinnetO. Induction and suppression of RNA silencing: Insights from viral infections. Nature Reviews Genetics, 2005, 6(3): 206-220

[74]

WangB, KobeissyF, GolpichM, CaiG, LiX, AbediR, HaskinsW, TanW, BennerSA, WangK. Aptamer Technologies in Neuroscience, Neuro-Diagnostics and Neuro-Medicine Development. Molecules, 2024, 29(5): 1124 K. W

[75]

WuY, WangR, LiuR, BaY, HuangH. The roles of histone modifications in metal-induced neurological disorders. Biological Trace Element Research, 2023, 201(1): 31-40

[76]

XieM, YuB. siRNA-directed DNA methylation in plants. Current Genomics, 2015, 16(1): 23-31

[77]

Zabala-Pardo, D., Gaines, T., Lamego, F. P., & Avila, L. A. (2022). RNAi as a tool for weed management: Challenges and opportunities. Advances in Weed Science, 40(spe 1), e020220096.

[78]

Zapletal, D., Kubicek, K., Svoboda, P., & Stefl, R. (2023). Dicer structure and function: Conserved and evolving features. EMBO Reports, 24(7), e57215.

[79]

Zhan, L., Zhang, Y., Wang, Y., Wang, A., Cheng, C., Zhao, J., Zhang, W., Lia, P., & Chen, J. (2024). A genome-scale deep learning model to predict gene expression changes of genetic perturbations from multiplex biological networks. ArXiv Preprint ArXiv:2403.02724.

[80]

ZhangR, XuW, ShaoS, WangQ. Gene silencing through CRISPR interference in bacteria: Current advances and future prospects. Frontiers in Microbiology, 2021, 12: 635227

[81]

ZhaoJ, GuoH. RNA silencing: From discovery and elucidation to application and perspectives. Journal of Integrative Plant Biology, 2022, 64(2): 476-498

[82]

ZhongV, ArchibaldBN, BrophyJAN. Transcriptional and post-transcriptional controls for tuning gene expression in plants. Current Opinion in Plant Biology, 2023, 71: 102315

[83]

ZhuY, ZhuL, WangX, JinH. RNA-based therapeutics: An overview and prospectus. Cell Death & Disease, 2022, 13(7): 644

[84]

ZulfiqarS, FarooqMA, ZhaoT, WangP, TabusamJ, WangY, XuanS, ZhaoJ, ChenX, ShenS. Virus-induced gene silencing (VIGS): A powerful tool for crop improvement and its advancement towards epigenetics. International Journal of Molecular Sciences, 2023, 24(6): 5608

AI Summary AI Mindmap
PDF

2657

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/