Genome-wide CRISPR screen reveals an uncharacterized spliceosome regulator as new candidate immunotherapy target

Abstract

Cancer immune evasion is orchestrated by tumor-intrinsic molecular constraints that remain incompletely defined. Here, we performed an in vivo genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen to catalogue gene regulatory determinants of immune evasion in cancer cells. We identify C9ORF50 as a novel splicing regulator whose inhibition profoundly sensitizes cancer to immune surveillance. Integrated multi-omics profiling reveals this intrinsically disordered protein exhibits liquid–liquid phase separation properties and forms nuclear condensates that colocalize with spliceosome components. Genetic ablation correlates with intron retention in multiple spliceosome components and cytoplasmic accumulation of double-stranded RNA, which is associated with type I interferon activation and enhances chemokine-mediated T cell recruitment. As a result, C9ORF50 inhibition amplifies tumor cell immunogenicity, enhancing T cell infiltration in poorly infiltrated tumors. Clinically, elevated C9ORF50 expression correlates with poor survival and diminished lymphoid infiltration across malignancies. Therapeutic targeting of C9ORF50 using RNA interference enhances T cell infiltration and suppresses tumor growth. Our work identifies C9ORF50 as a candidate therapeutic target that modulates RNA splicing and tumor immunity, suggesting splicing regulation as a potential strategy to enhance immunotherapy responses.

Keywords

antitumor immunity / C9ORF50 / CRISPR screen / intrinsically disordered protein / liquid–liquid phase separation / RNA splicing / therapeutic targets

References

[1] Dagher, Oula K., Robert D. Schwab, Shawna K. Brookens, and Avery D. Posey. 2023. “Advances in Cancer Immunotherapies.” Cell 186: 1814-1814.e1. https://doi.org/10.1016/j.cell.2023.02.039

[2] Wei, Yaohua, Feng Shen, Huidong Song, Ruifang Zhao, Weiyue Feng, Yue Pan, Xiaobo Li, et al. 2024. “The Challenge and Opportunity of Gut Microbiota-Targeted Nanomedicine for Colorectal Cancer Therapy.” iMeta 3: e213. https://doi.org/10.1002/imt2.213

[3] Kyrysyuk, Oleksandr, and Kai W. Wucherpfennig. 2023. “Designing Cancer Immunotherapies That Engage T Cells and NK Cells.” Annual Review of Immunology 41: 17-38. https://doi.org/10.1146/annurev-immunol-101921-044122

[4] Tang, Lu, Zhongpei Huang, Heng Mei, and Yu Hu. 2023. “Immunotherapy in Hematologic Malignancies: Achievements, Challenges and Future Prospects.” Signal Transduction and Targeted Therapy 8: 306. https://doi.org/10.1038/s41392-023-01521-5

[5] Wang, Liang, Jieyi Fan, Sifan Wu, Shilin Cheng, Junlong Zhao, Fan Fan, Chunchen Gao, et al. 2024. “LTBR Acts as a Novel Immune Checkpoint of Tumor-Associated Macrophages for Cancer Immunotherapy.” iMeta 3: e233. https://doi.org/10.1002/imt2.233

[6] Fan, Ting, Mingna Zhang, Jingxian Yang, Zhounan Zhu, Wanlu Cao, and Chunyan Dong. 2023. “Therapeutic Cancer Vaccines: Advancements, Challenges and Prospects.” Signal Transduction and Targeted Therapy 8: 450. https://doi.org/10.1038/s41392-023-01674-3

[7] Sadeghi Rad, Habib, James Monkman, Majid E. Warkiani, Rahul Ladwa, Ken O'Byrne, Nima Rezaei, and Arutha Kulasinghe. 2021. “Understanding the Tumor Microenvironment for Effective Immunotherapy.” Medicinal Research Reviews 41: 1474-1498. https://doi.org/10.1002/med.21765

[8] Yuan, Sujing, Renqiang Sun, Hao Shi, Nicole M. Chapman, Haoran Hu, Cliff Guy, Sherri Rankin, et al. 2025. “VDAC2 Loss Elicits Tumour Destruction and Inflammation for Cancer Therapy.” Nature 640: 1062-1071. https://doi.org/10.1038/s41586-025-08732-6

[9] Ghorani, Ehsan, Charles Swanton, and Sergio A. Quezada. 2023. “Cancer Cell-Intrinsic Mechanisms Driving Acquired Immune Tolerance.” Immunity 56: 2270-2295. https://doi.org/10.1016/j.immuni.2023.09.004

[10] Wellenstein, Max D., and Karin E. de Visser. 2018. “Cancer-Cell-Intrinsic Mechanisms Shaping the Tumor Immune Landscape.” Immunity 48: 399-416. https://doi.org/10.1016/j.immuni.2018.03.004

[11] Zhu, Mingrui, Yi Huang, Matthew E. Bender, Luc Girard, Rahul Kollipara, Buse Eglenen-Polat, Yujiro Naito, et al. 2021. “Evasion of Innate Immunity Contributes to Small Cell Lung Cancer Progression and Metastasis.” Cancer Research 81: 1813-1826. https://doi.org/10.1158/0008-5472.Can-20-2808

[12] Li, Yan-Ruide, Tyler Halladay, and Lili Yang. 2024. “Immune Evasion in Cell-Based Immunotherapy: Unraveling Challenges and Novel Strategies.” Journal of Biomedical Science 31: 5. https://doi.org/10.1186/s12929-024-00998-8

[13] van Weverwijk, Antoinette, and Karin E. de Visser. 2023. “Mechanisms Driving the Immunoregulatory Function of Cancer Cells.” Nature Reviews Cancer 23: 193-215. https://doi.org/10.1038/s41568-022-00544-4

[14] Joung, Julia, Paul C. Kirchgatterer, Ankita Singh, Jang H. Cho, Suchita P. Nety, Rebecca C. Larson, Rhiannon K. Macrae, et al. 2022. “CRISPR Activation Screen Identifies BCL-2 Proteins and B3GNT2 as Drivers of Cancer Resistance to T Cell-Mediated Cytotoxicity.” Nature Communications 13: 1606. https://doi.org/10.1038/s41467-022-29205-8

[15] Zhong, Chunge, Wen-Jie Jiang, Yingjia Yao, Zexu Li, You Li, Shengnan Wang, Xiaofeng Wang, et al. 2024. “CRISPR Screens Reveal Convergent Targeting Strategies Against Evolutionarily Distinct Chemoresistance in Cancer.” Nature Communications 15: 5502. https://doi.org/10.1038/s41467-024-49673-4

[16] Wei, Yiliang, Yu-Han Huang, Damianos S. Skopelitis, Shruti V. Iyer, Ana S. H. Costa, Zhaolin Yang, Melissa Kramer, et al. 2022. “SLC5A3-dependent Myo-Inositol Auxotrophy in Acute Myeloid Leukemia.” Cancer Discovery 12: 450-467. https://doi.org/10.1158/2159-8290.Cd-20-1849

[17] Chan, Edmond M., Tsukasa Shibue, James M. McFarland, Benjamin Gaeta, Mahmoud Ghandi, Nancy Dumont, Alfredo Gonzalez, et al. 2019. “WRN Helicase Is a Synthetic Lethal Target in Microsatellite Unstable Cancers.” Nature 568: 551-556. https://doi.org/10.1038/s41586-019-1102-x

[18] Klimeck, Leon, Thomas Heisser, Michael Hoffmeister, and Hermann Brenner. 2023. “Colorectal Cancer: A Health and Economic Problem.” Best Practice & Research Clinical Gastroenterology 66: 101839. https://doi.org/10.1016/j.bpg.2023.101839

[19] Kwok, Darwin W., Nicholas O. Stevers, Iñaki Etxeberria, Takahide Nejo, Maggie Colton Cove, Lee H. Chen, Jangham Jung, et al. 2025. “Tumour-Wide RNA Splicing Aberrations Generate Actionable Public Neoantigens.” Nature 693: 463-473. https://doi.org/10.1038/s41586-024-08552-0

[20] Cieśla, Maciej, Phuong Cao Thi Ngoc, Sowndarya Muthukumar, Gabriele Todisco, Magdalena Madej, Helena Fritz, Marios Dimitriou, et al. 2023. “m6A-Driven SF3B1 Translation Control Steers Splicing to Direct Genome Integrity and Leukemogenesis.” Molecular Cell 83: 1165-1179.e11. https://doi.org/10.1016/j.molcel.2023.02.024

[21] Deng, Ling, Li Liao, Yin-Ling Zhang, Shao-Ying Yang, Shu-Yuan Hu, Lisa Andriani, Yun-Xiao Ling, et al. 2024. “SF3A2 Promotes Progression and Cisplatin Resistance in Triple-Negative Breast Cancer via Alternative Splicing of MKRN1.” Science Advances 10: eadj4009. https://doi.org/10.1126/sciadv.adj4009

[22] Wan, Ledong, Kuan-Ting Lin, Mohammad Alinoor Rahman, Yuma Ishigami, Zhikai Wang, Mads A. Jensen, John E. Wilkinson, et al. 2023. “Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer.” Cancer Discovery 13: 1678-1695. https://doi.org/10.1158/2159-8290.Cd-22-1013

[23] Cohen-Eliav, Michal, Regina Golan-Gerstl, Zahava Siegfried, Claus L. Andersen, Kasper Thorsen, Torben F. Ørntoft, David Mu, and Rotem Karni. 2013. “The Splicing Factor SRSF6 Is Amplified and Is an Oncoprotein in Lung and Colon Cancers.” Journal of Pathology 229: 630-639. https://doi.org/10.1002/path.4129

[24] Steensma, David P., Martin Wermke, Virginia M. Klimek, Peter L. Greenberg, Patricia Font, Rami S. Komrokji, Jay Yang, et al. 2021. “Phase I First-In-Human Dose Escalation Study of the Oral SF3B1 Modulator H3B-8800 In Myeloid Neoplasms.” Leukemia 35: 3542-3550. https://doi.org/10.1038/s41375-021-01328-9

[25] Danson, S. J., P. Johnson, T. H. Ward, M. Dawson, O. Denneny, G. Dickinson, L. Aarons, et al. 2011. “Phase I Pharmacokinetic and Pharmacodynamic Study of the Bioreductive Drug RH1.” Annals of Oncology 22: 1653-1660. https://doi.org/10.1093/annonc/mdq638

[26] Corrionero, Anna, Belén Miñana, and Juan Valcárcel. 2011. “Reduced Fidelity of Branch Point Recognition and Alternative Splicing Induced by the Anti-Tumor Drug Spliceostatin A.” Genes and Development 25: 445-459. https://doi.org/10.1101/gad.2014311

[27] Darrigrand, Romain, Alison Pierson, Marine Rouillon, Dolor Renko, Mathilde Boulpicante, David Bouyssié, Emmanuelle Mouton-Barbosa, et al. 2021. “Isoginkgetin Derivative IP2 Enhances the Adaptive Immune Response Against Tumor Antigens.” Communications Biology 4: 269. https://doi.org/10.1038/s42003-021-01801-2

[28] Xu, Yuewei, Anke Nijhuis, and Hector C. Keun. 2022. “RNA-Binding Motif Protein 39 (RBM39): An Emerging Cancer Target.” British Journal of Pharmacology 179: 2795-2812. https://doi.org/10.1111/bph.15331

[29] Lu, Sydney X., Emma De Neef, James D. Thomas, Erich Sabio, Benoit Rousseau, Mathieu Gigoux, David A. Knorr, et al. 2021. “Pharmacologic Modulation of RNA Splicing Enhances Anti-Tumor Immunity.” Cell 184: 4032-4047.e31. https://doi.org/10.1016/j.cell.2021.05.038

[30] Shaw, Alice T., and Jeffrey A. Engelman. 2013. “ALK in Lung Cancer: Past, Present, and Future.” Journal of Clinical Oncology 31: 1105-1111. https://doi.org/10.1200/jco.2012.44.5353

[31] Lou, Lixin, Peng Zhang, Rongli Piao, and Yang Wang. 2019. “Salmonella Pathogenicity Island 1 (SPI-1) and Its Complex Regulatory Network.” Frontiers in Cellular and Infection Microbiology 9: 270. https://doi.org/10.3389/fcimb.2019.00270

[32] Bowling, Elizabeth A., Jarey H. Wang, Fade Gong, William Wu, Nicholas J. Neill, Ik Sun Kim, Siddhartha Tyagi, et al. 2021. “Spliceosome-Targeted Therapies Trigger an Antiviral Immune Response in Triple-Negative Breast Cancer.” Cell 184: 384-403.e21. https://doi.org/10.1016/j.cell.2020.12.031

[33] Ge, Ying, and Bo T. Porse. 2014. “The Functional Consequences of Intron Retention: Alternative Splicing Coupled to NMD as a Regulator of Gene Expression.” BioEssays 36: 236-243. https://doi.org/10.1002/bies.201300156

[34] Chen, Y. Grace, and Sun Hur. 2022. “Cellular Origins of dsRNA, Their Recognition and Consequences.” Nature Reviews Molecular Cell Biology 23: 286-301. https://doi.org/10.1038/s41580-021-00430-1

[35] Chang, Aaron Y., Yu Jerry Zhou, Sharanya Iyengar, Piotr W. Pobiarzyn, Pavel Tishchenko, Kesha M. Shah, Heather Wheeler, et al. 2021. “Modulation of SF3B1 in the Pre-mRNA Spliceosome Induces a RIG-I-Dependent Type I IFN Response.” Journal of Biological Chemistry 297: 101277. https://doi.org/10.1016/j.jbc.2021.101277

[36] He, Jianfeng, Yongyi Zhu, Zichao Tian, Mengqin Liu, Anmin Gao, Wangmi Fu, Fei Lu, et al. 2025. “ZBP1 Senses Spliceosome Stress Through Z-RNA: DNA Hybrid Recognition.” Molecular Cell 85: 1790-1805.e7. https://doi.org/10.1016/j.molcel.2025.04.004

[37] Lei, Xin, Indu Khatri, Tom de Wit, Iris de Rink, Marja Nieuwland, Ron Kerkhoven, Hans van Eenennaam, et al. 2023. “CD4⁺ Helper T Cells Endow cDC1 With Cancer-Impeding Functions in the Human Tumor Micro-Environment.” Nature Communications 14: 217. https://doi.org/10.1038/s41467-022-35615-5

[38] Heras-Murillo, Ignacio, Diego Mañanes, Pablo Munné, Vanessa Núñez, Jessica Herrera, Mauro Catalá-Montoro, Maite Alvarez, et al. 2025. “Immunotherapy With Conventional Type-1 Dendritic Cells Induces Immune Memory and Limits Tumor Relapse.” Nature Communications 16: 3369. https://doi.org/10.1038/s41467-025-58289-1

[39] Sistigu, Antonella, Takahiro Yamazaki, Erika Vacchelli, Kariman Chaba, David P. Enot, Julien Adam, Ilio Vitale, et al. 2014. “Cancer Cell-Autonomous Contribution of Type I Interferon Signaling to the Efficacy of Chemotherapy.” Nature Medicine 20: 1301-1309. https://doi.org/10.1038/nm.3708

[40] Luo, Ce, Rui Zhang, Rui Guo, Lijian Wu, Teng Xue, Yufeng He, Yiteng Jin, et al. 2025. “Integrated Computational Analysis Identifies Therapeutic Targets With Dual Action in Cancer Cells and T Cells.” Immunity 58: 745-765.e9. https://doi.org/10.1016/j.immuni.2025.02.007

[41] Li, Hui, Guodong Zhao, Yahui Guo, Yu Fang, Kai Wang, Yong Ma, Chenxi Feng, et al. 2022. “Feasibility and Reproducibility of a Plasma-Based Multiplex DNA Methylation Assay for Early Detection of Gastric Cancer.” Pathology-Research and Practice 238: 154086. https://doi.org/10.1016/j.prp.2022.154086

[42] Cao, Yaping, Guodong Zhao, Mufa Yuan, Xiaoyu Liu, Yong Ma, Yang Cao, Bei Miao, et al. 2021. “KCNQ5 and C9orf50 Methylation in Stool DNA for Early Detection of Colorectal Cancer.” Frontiers in Oncoogy. 10: 621295. https://doi.org/10.3389/fonc.2020.621295

[43] Calabretta, Sara, and Stéphane Richard. 2015. “Emerging Roles of Disordered Sequences in RNA-Binding Proteins.” Trends in Biochemical Sciences 40: 662-672. https://doi.org/10.1016/j.tibs.2015.08.012

[44] Reber, Stefan, Daniel Jutzi, Helen Lindsay, Anny Devoy, Jonas Mechtersheimer, Brunno Rocha Levone, Michal Domanski, et al. 2021. “The Phase Separation-Dependent FUS Interactome Reveals Nuclear and Cytoplasmic Function of Liquid-Liquid Phase Separation.” Nucleic Acids Research 49: 7713-7731. https://doi.org/10.1093/nar/gkab582

[45] Peng, Qiu, Lujuan Wang, Ying Long, Hao Tian, Xuemeng Xu, Zongyao Ren, Yaqian Han, et al. 2025. “SRSF9 Mediates Oncogenic RNA Splicing of SLC37A4 Via Liquid-Liquid Phase Separation to Promote Oral Cancer Progression.” Journal of Advanced Research. In press. https://doi.org/10.1016/j.jare.2025.03.013

[46] Möller, Emely, Viviane Praz, Sanalkumar Rajendran, Rui Dong, Alexandra Cauderay, Yu-Hang Xing, Lukuo Lee, et al. 2022. “EWSR1-ATF1 Dependent 3D Connectivity Regulates Oncogenic and Differentiation Programs in Clear Cell Sarcoma.” Nature Communications 13: 2267. https://doi.org/10.1038/s41467-022-29910-4

[47] Gong, Helong, Busheng Xue, Jinlong Ru, Guoqing Pei, and Yan Li. 2023. “Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.” Cancers 15: 4035. https://doi.org/10.3390/cancers15164035

[48] Climente-González, Héctor, Eduard Porta-Pardo, Adam Godzik, and Eduardo Eyras. 2017. “The Functional Impact of Alternative Splicing in Cancer.” Cell Rep. 20: 2215-2226. https://doi.org/10.1016/j.celrep.2017.08.012

[49] Bonnal, Sophie C., Irene López-Oreja, and Juan Valcárcel. 2020. “Roles and Mechanisms of Alternative Splicing in Cancer—Implications for Care.” Nature Reviews Clinical Oncology 17: 457-474. https://doi.org/10.1038/s41571-020-0350-x

[50] De Maio, Antonia, Hari Krishna Yalamanchili, Carolyn J. Adamski, Vincenzo A. Gennarino, Zhandong Liu, Jun Qin, Sung Y. Jung, et al. 2018. “RBM17 Interacts with U2SURP and CHERP to Regulate Expression and Splicing of RNA-Processing Proteins.” Cell Reports 25: 726-736.e7. https://doi.org/10.1016/j.celrep.2018.09.041

[51] Zhao, Zongmin, Anvay Ukidve, Jayoung Kim, and Samir Mitragotri. 2020. “Targeting Strategies for Tissue-Specific Drug Delivery.” Cell 181: 151-167. https://doi.org/10.1016/j.cell.2020.02.001

[52] Duff, Michael O., Sara Olson, Xintao Wei, Sandra C. Garrett, Ahmad Osman, Mohan Bolisetty, Alex Plocik, Susan E. Celniker, and Brenton R. Graveley. 2015. “Genome-Wide Identification of Zero Nucleotide Recursive Splicing in Drosophila.” Nature 521: 376-379. https://doi.org/10.1038/nature14475

[53] Wu, Kejia, Hanlun Jiang, Derrick R. Hicks, Caixuan Liu, Edin Muratspahić, Theresa A. Ramelot, Yuexuan Liu, et al. 2025. “Design of Intrinsically Disordered Region Binding Proteins.” Science 389: eadr8063. https://doi.org/10.1126/science.adr8063

[54] Wu, Yusheng, Wenwei Zhao, Yang Liu, Xiangtian Tan, Xin Li, Qin Zou, Zhengtao Xiao, et al. 2018. “Function of HNRNPC in Breast Cancer Cells by Controlling the dsRNA-Induced Interferon Response.” EMBO Journal 37: e99017. https://doi.org/10.15252/embj.201899017

[55] Di Giorgio, Eros, Liliana Ranzino, Vanessa Tolotto, Emiliano Dalla, Matteo Burelli, Nicolò Gualandi, and Claudio Brancolini. 2024. “Transcription of Endogenous Retroviruses in Senescent Cells Contributes to the Accumulation of Double-Stranded RNAs That Trigger an Anti-Viral Response That Reinforces Senescence.” Cell Death Disease 15: 157. https://doi.org/10.1038/s41419-024-06548-2

[56] Parang, Bobak, Caitlyn W. Barrett, and Christopher S. Williams. 2016. “AOM/DSS Model of Colitis-Associated Cancer.” In Gastrointestinal Physiology and Diseases: Methods and Protocols (pp. 297-307). Springer. https://doi.org/10.1007/978-1-4939-3603-8_26

[57] Li, Wei, Han Xu, Tengfei Xiao, Le Cong, Michael I. Love, Feng Zhang, Rafael A. Irizarry, et al. 2014. ““MAGeCK Enables Robust Identification of Essential Genes from Genome-Scale CRISPR/Cas9 Knockout Screens.” Genome Biology 15: 554. https://doi.org/10.1186/s13059-014-0554-4

[58] Li, Rui-Hua, Tian Tian, Qi-Wei Ge, Xin-Yu He, Cheng-Yu Shi, Jun-Hong Li, Zhen Zhang, et al. 2021. “A Phosphatidic Acid-Binding lncRNA SNHG9 Facilitates LATS1 Liquid-Liquid Phase Separation to Promote Oncogenic YAP Signaling.” Cell Research 31: 1088-1105. https://doi.org/10.1038/s41422-021-00530-9

[59] Love, Michael I., Wolfgang Huber, and Simon Anders. 2014. “Moderated Estimation of Fold Change and Dispersion for RNA-seq Data With DESeq2.” Genome Biology 15: 550. https://doi.org/10.1186/s13059-014-0550-8

[60] Wu, Tianzhi, Erqiang Hu, Shuangbin Xu, Meijun Chen, Pingfan Guo, Zehan Dai, Tingze Feng, et al. 2021. “clusterProfiler 4.0: A Universal Enrichment Tool for Interpreting Omics Data.” The Innovation 2: 100141. https://doi.org/10.1016/j.xinn.2021.100141

[61] Grandi, Fiorella C., Hailey Modi, Lucas Kampman, and M Ryan Corces. 2022. “Chromatin Accessibility Profiling by ATAC-seq.” Nat. Protoc. 17: 1518-1552. https://doi.org/10.1038/s41596-022-00692-9

[62] Keene, Jack D., Jordan M. Komisarow, and Matthew B. Friedersdorf. 2006. “RIP-Chip: the Isolation and Identification of mRNAs, microRNAs and Protein Components of Ribonucleoprotein Complexes From Cell Extracts.” Nat. Protoc. 1: 302-307. https://doi.org/10.1038/nprot.2006.47

[63] Wang, Guangchuan, Ryan D. Chow, Lvyun Zhu, Zhigang Bai, Lupeng Ye, Feifei Zhang, Paul A. Renauer, et al. 2020. “CRISPR-GEMM Pooled Mutagenic Screening Identifies KMT2D as a Major Modulator of Immune Checkpoint Blockade.” Cancer Discovery 10: 1912-1933. https://doi.org/10.1158/2159-8290.Cd-19-1448

[64] Wang, Ruoxing, Jundi Wang, Amber M. Paul, Dhiraj Acharya, Fengwei Bai, Faqing Huang, and Yan-Lin Guo. 2013. “Mouse Embryonic Stem Cells Are Deficient in Type I Interferon Expression in Response to Viral Infections and Double-Stranded RNA.” Journal of Biological Chemistry 288: 15926-15936. https://doi.org/10.1074/jbc.M112.421438

[65] Yan, Keqin, Weiwei Zhu, Lili Yu, Nan Li, Xiaoyan Zhang, Peipei Liu, Qiaoyuan Chen, Yongmei Chen, and Daishu Han. 2013. “Toll-Like Receptor 3 and RIG-I-Like Receptor Activation Induces Innate Antiviral Responses in Mouse Ovarian Granulosa Cells.” Molecular and Cellular Endocrinology 372: 73-85. https://doi.org/10.1016/j.mce.2013.03.027

[66] Akabane-Nakata, Masaaki, Namrata D. Erande, Pawan Kumar, Rohan Degaonkar, Jason A. Gilbert, June Qin, Martha Mendez, et al. 2021. “siRNAs Containing 2′-fluorinated Northern-Methanocarbacyclic (2′-F-NMC) Nucleotides: In Vitro and In Vivo RNAi Activity and Inability of Mitochondrial Polymerases to Incorporate 2′-F-NMC NTPs.” Nucleic Acids Res. 49: 2435-2449. https://doi.org/10.1093/nar/gkab050

[67] Darling, April, and Vladimir Uversky. 2017. “Intrinsic Disorder in Proteins With Pathogenic Repeat Expansions.” Molecules 22: 2027. https://doi.org/10.3390/molecules22122027

[68] Kulkarni, Prakash, and Vladimir N. Uversky. 2018. “Intrinsically Disordered Proteins and the Janus Challenge.” Biomolecules 8: 179. https://doi.org/10.3390/biom8040179

[69] Borgan, Ørnulf. 2001. “Modeling Survival Data: Extending the Cox Model. Terry M. Therneau and Patricia M. Grambsch, Springer-Verlag, New York, 2000. No. of Pages: Xiii+ 350. ISBN 0-387-98784-3.” Statistics in Medicine 20: 2053-2054. https://doi.org/10.1002/sim.956

RIGHTS & PERMISSIONS

2025 The Author(s). iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.