{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:48:07Z","timestamp":1792522087134,"version":"4.5.0"},"posted":{"date-parts":[[2025,1,2]]},"group-title":"Molecular Biology","reference-count":129,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Facioscapulohumeral muscular dystrophy (FSHD) is a potentially devastating muscle disease caused by de-repression of the toxic\n                  <jats:italic>DUX4<\/jats:italic>\n                  gene in skeletal muscle. FSHD patients may benefit from\n                  <jats:italic>DUX4<\/jats:italic>\n                  inhibition therapies, and although several experimental strategies to reduce\n                  <jats:italic>DUX4<\/jats:italic>\n                  levels in skeletal muscle are being developed, no approved disease modifying therapies currently exist. We developed a CRISPR-Cas13b system that cleaves\n                  <jats:italic>DUX4<\/jats:italic>\n                  mRNA and reduces DUX4 protein level, protects cells from DUX4-mediated death, and reduces FSHD-associated biomarkers\n                  <jats:italic>in vitro<\/jats:italic>\n                  .\n                  <jats:italic>In vivo<\/jats:italic>\n                  delivery of the CRISPR-Cas13b system with adeno-associated viral vectors reduced acute damage caused by high\n                  <jats:italic>DUX4<\/jats:italic>\n                  levels in a mouse model of severe FSHD. However, protection was not sustained over time, with decreases in Cas13b and guide RNA levels between 8 weeks and 6 months after injection. In addition, wild-type mice injected with AAV6.Cas13b showed muscle inflammation with infiltrates containing Cas13b-responsive CD8+ cytotoxic T cells. Our RNA-seq data confirmed that several immune response pathways were significantly increased in human FSHD myoblasts transfected with Cas13b. Overall, our findings suggest that CRISPR-Cas13b is highly effective for\n                  <jats:italic>DUX4<\/jats:italic>\n                  silencing but successful implementation of CRISPR\/Cas13-based gene therapies may require strategies to mitigate immune responses.\n                <\/jats:p>","DOI":"10.1101\/2024.12.18.629250","type":"posted-content","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T15:10:17Z","timestamp":1735830617000},"source":"Crossref","is-referenced-by-count":4,"title":["Sustained efficacy of CRISPR-Cas13b gene therapy for FSHD is challenged by immune response to Cas13b"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0198-5492","authenticated-orcid":false,"given":"Afrooz","family":"Rashnonejad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal","family":"Farea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gholamhossein","family":"Amini-Chermahini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5991-9706","authenticated-orcid":false,"given":"Gerald","family":"Coulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5212-2259","authenticated-orcid":false,"given":"Armando","family":"Villalta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver D.","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott Q.","family":"Harper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025010705401119000_2024.12.18.629250v1.1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000797"},{"key":"2025010705401119000_2024.12.18.629250v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2020.09.008"},{"key":"2025010705401119000_2024.12.18.629250v1.3","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-00675-3"},{"key":"2025010705401119000_2024.12.18.629250v1.4","doi-asserted-by":"publisher","DOI":"10.1212\/CON.0000000000000399"},{"key":"2025010705401119000_2024.12.18.629250v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2003.07.001"},{"key":"2025010705401119000_2024.12.18.629250v1.6","doi-asserted-by":"crossref","unstructured":"R. Tawil , S. M. van der Maarel , S. J. Tapscott , Facioscapulohumeral dystrophy: the path to consensus on pathophysiology. Skelet Muscle 4, 12 (2014).","DOI":"10.1186\/2044-5040-4-12"},{"key":"2025010705401119000_2024.12.18.629250v1.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8123-2"},{"key":"2025010705401119000_2024.12.18.629250v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25991"},{"key":"2025010705401119000_2024.12.18.629250v1.9","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000008123"},{"key":"2025010705401119000_2024.12.18.629250v1.10","doi-asserted-by":"crossref","unstructured":"M. Ghasemi , C. P. Emerson, Jr. , L. J. Hayward , Outcome Measures in Facioscapulohumeral Muscular Dystrophy Clinical Trials. Cells 11, (2022).","DOI":"10.3390\/cells11040687"},{"key":"2025010705401119000_2024.12.18.629250v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2018.04.013"},{"key":"2025010705401119000_2024.12.18.629250v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.04.002"},{"key":"2025010705401119000_2024.12.18.629250v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.201"},{"key":"2025010705401119000_2024.12.18.629250v1.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708659104"},{"key":"2025010705401119000_2024.12.18.629250v1.15","doi-asserted-by":"crossref","unstructured":"C. R. Giesige , L. M. Wallace , K. N. Heller , J. O. Eidahl , N. Y. Saad , A. M. Fowler , N. K. Pyne , M. Al-Kharsan , A. Rashnonejad , G. A. Chermahini , J. S. Domire , D. Mukweyi , S. E. Garwick-Coppens , S. M. Guckes , K. J. McLaughlin , K. Meyer , L. R. Rodino-Klapac , S. Q. Harper , AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD. JCI Insight 3, (2018).","DOI":"10.1172\/jci.insight.123538"},{"key":"2025010705401119000_2024.12.18.629250v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2454"},{"key":"2025010705401119000_2024.12.18.629250v1.17","doi-asserted-by":"publisher","DOI":"10.1126\/science.1189044"},{"key":"2025010705401119000_2024.12.18.629250v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2011.01.001"},{"key":"2025010705401119000_2024.12.18.629250v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22275"},{"key":"2025010705401119000_2024.12.18.629250v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3844"},{"key":"2025010705401119000_2024.12.18.629250v1.21","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp180"},{"key":"2025010705401119000_2024.12.18.629250v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-35150-8"},{"key":"2025010705401119000_2024.12.18.629250v1.23","doi-asserted-by":"publisher","DOI":"10.1261\/rna.070177.118"},{"key":"2025010705401119000_2024.12.18.629250v1.24","doi-asserted-by":"crossref","unstructured":"T. Arends , H. Tsuchida , R. O. Adeyemi , S. J. Tapscott , DUX4-induced HSATII transcription causes KDM2A\/B-PRC1 nuclear foci and impairs DNA damage response. J Cell Biol 223, (2024).","DOI":"10.1083\/jcb.202303141"},{"key":"2025010705401119000_2024.12.18.629250v1.25","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0224"},{"key":"2025010705401119000_2024.12.18.629250v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2016.12.007"},{"key":"2025010705401119000_2024.12.18.629250v1.27","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv315"},{"key":"2025010705401119000_2024.12.18.629250v1.28","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy293"},{"key":"2025010705401119000_2024.12.18.629250v1.29","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw141"},{"key":"2025010705401119000_2024.12.18.629250v1.30","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddad186"},{"key":"2025010705401119000_2024.12.18.629250v1.31","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds467"},{"key":"2025010705401119000_2024.12.18.629250v1.32","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy348"},{"key":"2025010705401119000_2024.12.18.629250v1.33","first-page":"386","article-title":"Testing the effects of FSHD candidate gene expression in vertebrate muscle development","volume":"3","year":"2010","journal-title":"Int J Clin Exp Pathol"},{"key":"2025010705401119000_2024.12.18.629250v1.34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150938"},{"key":"2025010705401119000_2024.12.18.629250v1.35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003415"},{"key":"2025010705401119000_2024.12.18.629250v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.07.056"},{"key":"2025010705401119000_2024.12.18.629250v1.37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151467"},{"key":"2025010705401119000_2024.12.18.629250v1.38","doi-asserted-by":"crossref","unstructured":"D. Bosnakovski , S. S. K. Chan , O. O. Recht , L. M. Hartweck , C. J. Gustafson , L. L. Athman , D. A. Lowe , M. Kyba , Muscle pathology from stochastic low level DUX4 expression in an FSHD mouse model. Nat Commun 8, 550 (2017).","DOI":"10.1038\/s41467-017-00730-1"},{"key":"2025010705401119000_2024.12.18.629250v1.39","doi-asserted-by":"publisher","DOI":"10.1172\/JCI133303"},{"key":"2025010705401119000_2024.12.18.629250v1.40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192657"},{"key":"2025010705401119000_2024.12.18.629250v1.41","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu028"},{"key":"2025010705401119000_2024.12.18.629250v1.42","doi-asserted-by":"publisher","DOI":"10.1101\/2023.11.17.567590"},{"key":"2025010705401119000_2024.12.18.629250v1.43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026820"},{"key":"2025010705401119000_2024.12.18.629250v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.200"},{"key":"2025010705401119000_2024.12.18.629250v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.05.020"},{"key":"2025010705401119000_2024.12.18.629250v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.12.001"},{"key":"2025010705401119000_2024.12.18.629250v1.47","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw015"},{"key":"2025010705401119000_2024.12.18.629250v1.48","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.111"},{"key":"2025010705401119000_2024.12.18.629250v1.49","doi-asserted-by":"crossref","unstructured":"E. Ansseau , C. Vanderplanck , A. Wauters , S. Q. Harper , F. Copp\u00e9e , A. Belayew , Antisense Oligonucleotides Used to Target the DUX4 mRNA as Therapeutic Approaches in FaciosScapuloHumeral Muscular Dystrophy (FSHD). Genes (Basel ) 8, (2017).","DOI":"10.3390\/genes8030093"},{"key":"2025010705401119000_2024.12.18.629250v1.50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1909649117"},{"key":"2025010705401119000_2024.12.18.629250v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.12.004"},{"key":"2025010705401119000_2024.12.18.629250v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2017.12.005"},{"key":"2025010705401119000_2024.12.18.629250v1.53","doi-asserted-by":"crossref","unstructured":"T. Kakimoto , A. Ogasawara , K. Ishikawa , T. Kurita , K. Yoshida , S. Harada , T. Nonaka , Y. Inoue , K. Uchida , T. Tateoka , T. Ohta , S. Kumagai , T. Sasaki , H. Aihara , A Systemically Administered Unconjugated Antisense Oligonucleotide Targeting DUX4 Improves Muscular Injury and Motor Function in FSHD Model Mice. Biomedicines 11, (2023).","DOI":"10.3390\/biomedicines11092339"},{"key":"2025010705401119000_2024.12.18.629250v1.54","doi-asserted-by":"crossref","unstructured":"N. Lu-Nguyen , G. Dickson , A. Malerba , L. Popplewell , Long-Term Systemic Treatment of a Mouse Model Displaying Chronic FSHD-like Pathology with Antisense Therapeutics That Inhibit DUX4 Expression. Biomedicines 10, (2022).","DOI":"10.3390\/biomedicines10071623"},{"key":"2025010705401119000_2024.12.18.629250v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.09.010"},{"key":"2025010705401119000_2024.12.18.629250v1.56","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2020.0862"},{"key":"2025010705401119000_2024.12.18.629250v1.57","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab136"},{"key":"2025010705401119000_2024.12.18.629250v1.58","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26668"},{"key":"2025010705401119000_2024.12.18.629250v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.10.028"},{"key":"2025010705401119000_2024.12.18.629250v1.60","doi-asserted-by":"crossref","unstructured":"J. Cohen , S. Huang , K. E. Koczwara , K. T. Woods , V. Ho , K. G. Woodman , J. L. Arbiser , K. Daman , M. Lek , C. P. Emerson, Jr. , A. M. DeSimone , Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism. Cell Death Dis 14, 749 (2023).","DOI":"10.1038\/s41419-023-06257-2"},{"key":"2025010705401119000_2024.12.18.629250v1.61","doi-asserted-by":"publisher","DOI":"10.1038\/nature24049"},{"key":"2025010705401119000_2024.12.18.629250v1.62","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaq0180"},{"key":"2025010705401119000_2024.12.18.629250v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.12.023"},{"key":"2025010705401119000_2024.12.18.629250v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.06.029"},{"key":"2025010705401119000_2024.12.18.629250v1.65","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.12.2037"},{"key":"2025010705401119000_2024.12.18.629250v1.66","doi-asserted-by":"crossref","unstructured":"A. M. DeSimone , J. Cohen , M. Lek , A. Lek , Cellular and animal models for facioscapulohumeral muscular dystrophy. Dis Model Mech 13, (2020).","DOI":"10.1242\/dmm.046904"},{"key":"2025010705401119000_2024.12.18.629250v1.67","doi-asserted-by":"crossref","unstructured":"S. Das , B. P. Chadwick , CRISPR mediated targeting of DUX4 distal regulatory element represses DUX4 target genes dysregulated in Facioscapulohumeral muscular dystrophy. Sci Rep 11, 12598 (2021).","DOI":"10.1038\/s41598-021-92096-0"},{"key":"2025010705401119000_2024.12.18.629250v1.68","doi-asserted-by":"crossref","unstructured":"R. Joubert , V. Mariot , M. Charpentier , J. P. Concordet , J. Dumonceaux , Gene Editing Targeting the DUX4 Polyadenylation Signal: A Therapy for FSHD? J Pers Med 11, (2020).","DOI":"10.3390\/jpm11010007"},{"key":"2025010705401119000_2024.12.18.629250v1.69","doi-asserted-by":"crossref","unstructured":"S. Bandaru , M. H. Tsuji , Y. Shimizu , K. Usami , S. Lee , N. K. Takei , K. Yoshitome , Y. Nishimura , T. Otsuki , T. Ito , Structure-based design of gRNA for Cas13. Sci Rep 10, 11610 (2020).","DOI":"10.1038\/s41598-020-68459-4"},{"key":"2025010705401119000_2024.12.18.629250v1.70","doi-asserted-by":"crossref","unstructured":"H. C. Kuo , J. Prupes , C. W. Chou , I. J. Finkelstein , Massively parallel profiling of RNA-targeting CRISPR-Cas13d. Nat Commun 15, 498 (2024).","DOI":"10.1038\/s41467-024-44738-w"},{"key":"2025010705401119000_2024.12.18.629250v1.71","doi-asserted-by":"crossref","unstructured":"X. Guo , J. A. Rahman , H. H. Wessels , A. M\u00e9ndez-Mancilla , D. Haro , X. Chen , N. E. Sanjana , Transcriptome-wide Cas13 guide RNA design for model organisms and viral RNA pathogens. Cell Genom 1, (2021).","DOI":"10.1016\/j.xgen.2021.100001"},{"key":"2025010705401119000_2024.12.18.629250v1.72","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds284"},{"key":"2025010705401119000_2024.12.18.629250v1.73","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001181"},{"key":"2025010705401119000_2024.12.18.629250v1.74","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu251"},{"key":"2025010705401119000_2024.12.18.629250v1.75","first-page":"4577","article-title":"Mouse Dux is myotoxic and shares partial functional homology with its human paralog DUX4","volume":"25","year":"2016","journal-title":"Hum Mol Genet"},{"key":"2025010705401119000_2024.12.18.629250v1.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.11.013"},{"key":"2025010705401119000_2024.12.18.629250v1.77","first-page":"4419","article-title":"Model systems of DUX4 expression recapitulate the transcriptional profile of FSHD cells","volume":"25","year":"2016","journal-title":"Hum Mol Genet"},{"key":"2025010705401119000_2024.12.18.629250v1.78","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy400"},{"key":"2025010705401119000_2024.12.18.629250v1.79","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064691"},{"key":"2025010705401119000_2024.12.18.629250v1.80","doi-asserted-by":"crossref","unstructured":"A. Lek , Y. Zhang , K. G. Woodman , S. Huang , A. M. DeSimone , J. Cohen , V. Ho , J. Conner , L. Mead , A. Kodani , A. Pakula , N. Sanjana , O. D. King , P. L. Jones , K. R. Wagner , M. Lek , L. M. Kunkel , Applying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy. Sci Transl Med 12, (2020).","DOI":"10.1126\/scitranslmed.aay0271"},{"key":"2025010705401119000_2024.12.18.629250v1.81","doi-asserted-by":"crossref","unstructured":"Q. Wang , X. Liu , J. Zhou , C. Yang , G. Wang , Y. Tan , Y. Wu , S. Zhang , K. Yi , C. Kang , The CRISPR-Cas13a Gene-Editing System Induces Collateral Cleavage of RNA in Glioma Cells. Adv Sci (Weinh ) 6, 1901299 (2019).","DOI":"10.1002\/advs.201901299"},{"key":"2025010705401119000_2024.12.18.629250v1.82","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201905751"},{"key":"2025010705401119000_2024.12.18.629250v1.83","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03886-5"},{"key":"2025010705401119000_2024.12.18.629250v1.84","doi-asserted-by":"crossref","unstructured":"P. Shi , M. R. Murphy , A. O. Aparicio , J. S. Kesner , Z. Fang , Z. Chen , A. Trehan , Y. Guo , X. Wu , Collateral activity of the CRISPR\/RfxCas13d system in human cells. Commun Biol 6, 334 (2023).","DOI":"10.1038\/s42003-023-04708-2"},{"key":"2025010705401119000_2024.12.18.629250v1.85","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-023-02860-w"},{"key":"2025010705401119000_2024.12.18.629250v1.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.033"},{"key":"2025010705401119000_2024.12.18.629250v1.87","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2012.01647.x"},{"key":"2025010705401119000_2024.12.18.629250v1.88","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0456-9"},{"key":"2025010705401119000_2024.12.18.629250v1.89","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.68"},{"key":"2025010705401119000_2024.12.18.629250v1.90","doi-asserted-by":"publisher","DOI":"10.1016\/j.mporth.2009.03.001"},{"key":"2025010705401119000_2024.12.18.629250v1.91","doi-asserted-by":"publisher","DOI":"10.4324\/9780203483671"},{"key":"2025010705401119000_2024.12.18.629250v1.92","doi-asserted-by":"crossref","unstructured":"S. LoRusso , N. E. Johnson , M. P. McDermott , K. Eichinger , R. J. Butterfield , E. Carraro , K. Higgs , L. Lewis , K. Mul , S. Sacconi , V. A. Sansone , P. Shieh , B. van Engelen , K. Wagner , L. Wang , J. M. Statland , R. Tawil , Clinical trial readiness to solve barriers to drug development in FSHD (ReSolve): protocol of a large, international, multi-center prospective study. BMC Neurol 19, 224 (2019).","DOI":"10.1186\/s12883-019-1452-x"},{"key":"2025010705401119000_2024.12.18.629250v1.93","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.07.009"},{"key":"2025010705401119000_2024.12.18.629250v1.94","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00073-5"},{"key":"2025010705401119000_2024.12.18.629250v1.95","doi-asserted-by":"crossref","unstructured":"J. Kools , N. Voermans , J. G. Jiang , O. Mitelman , M. L. Mellion , V. Ramana , B. G. M. van Engelen , An open-label pilot study of losmapimod to evaluate the safety, tolerability, and changes in biomarker and clinical outcome assessments in participants with facioscapulohumeral muscular dystrophy type 1. J Neurol Sci 462, 123096 (2024).","DOI":"10.1016\/j.jns.2024.123096"},{"key":"2025010705401119000_2024.12.18.629250v1.96","doi-asserted-by":"crossref","unstructured":"C. M. Brennan , C. P. Emerson, Jr. , J. Owens , N. Christoforou , p38 MAPKs - roles in skeletal muscle physiology, disease mechanisms, and as potential therapeutic targets. JCI Insight 6, (2021).","DOI":"10.1172\/jci.insight.149915"},{"key":"2025010705401119000_2024.12.18.629250v1.97","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.119.259663"},{"key":"2025010705401119000_2024.12.18.629250v1.98","doi-asserted-by":"crossref","unstructured":"Y. Zhang , T. M. Nguyen , X. O. Zhang , L. Wang , T. Phan , J. G. Clohessy , P. P. Pandolfi , Optimized RNA-targeting CRISPR\/Cas13d technology outperforms shRNA in identifying functional circRNAs. Genome Biol 22, 41 (2021).","DOI":"10.1186\/s13059-021-02263-9"},{"key":"2025010705401119000_2024.12.18.629250v1.99","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01848-6"},{"key":"2025010705401119000_2024.12.18.629250v1.100","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0326-x"},{"key":"2025010705401119000_2024.12.18.629250v1.101","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26830-7"},{"key":"2025010705401119000_2024.12.18.629250v1.102","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.05.007"},{"key":"2025010705401119000_2024.12.18.629250v1.103","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05843-9"},{"key":"2025010705401119000_2024.12.18.629250v1.104","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09693-x"},{"key":"2025010705401119000_2024.12.18.629250v1.105","doi-asserted-by":"crossref","unstructured":"F. Li , H. Zhao , L. Sui , F. Yin , X. Liu , G. Guo , J. Li , Y. Jiang , W. Cui , Z. Shan , H. Zhou , L. Wang , X. Qiao , L. Tang , X. Wang , Y. Li , Assessing immunogenicity of CRISPR-NCas9 engineered strain against porcine epidemic diarrhea virus. Appl Microbiol Biotechnol 108, 248 (2024).","DOI":"10.1007\/s00253-023-12989-0"},{"key":"2025010705401119000_2024.12.18.629250v1.106","doi-asserted-by":"publisher","DOI":"10.1089\/crispr.2021.0142"},{"key":"2025010705401119000_2024.12.18.629250v1.107","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-023-00641-2"},{"key":"2025010705401119000_2024.12.18.629250v1.108","doi-asserted-by":"publisher","DOI":"10.1089\/crispr.2021.0076"},{"key":"2025010705401119000_2024.12.18.629250v1.109","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01419-7"},{"key":"2025010705401119000_2024.12.18.629250v1.110","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-023-01279-5"},{"key":"2025010705401119000_2024.12.18.629250v1.111","doi-asserted-by":"publisher","DOI":"10.1038\/nature16526"},{"key":"2025010705401119000_2024.12.18.629250v1.112","doi-asserted-by":"crossref","unstructured":"M. Naeem , S. Majeed , M. Z. Hoque , I. Ahmad , Latest Developed Strategies to Minimize the Off-Target Effects in CRISPR-Cas-Mediated Genome Editing. Cells 9, (2020).","DOI":"10.3390\/cells9071608"},{"key":"2025010705401119000_2024.12.18.629250v1.113","doi-asserted-by":"crossref","unstructured":"N. Javaid , S. Choi , CRISPR\/Cas System and Factors Affecting Its Precision and Efficiency. Front Cell Dev Biol 9, 761709 (2021).","DOI":"10.3389\/fcell.2021.761709"},{"key":"2025010705401119000_2024.12.18.629250v1.114","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.07.004"},{"key":"2025010705401119000_2024.12.18.629250v1.115","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1199"},{"key":"2025010705401119000_2024.12.18.629250v1.116","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03765-1"},{"key":"2025010705401119000_2024.12.18.629250v1.117","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1325-9"},{"key":"2025010705401119000_2024.12.18.629250v1.118","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27430-1"},{"key":"2025010705401119000_2024.12.18.629250v1.119","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2571"},{"key":"2025010705401119000_2024.12.18.629250v1.120","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2025010705401119000_2024.12.18.629250v1.121","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2025010705401119000_2024.12.18.629250v1.122","first-page":"1438","article-title":"From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline","volume":"5","year":"2016","journal-title":"F1000Res"},{"key":"2025010705401119000_2024.12.18.629250v1.123","doi-asserted-by":"publisher","DOI":"10.2307\/2346101"},{"key":"2025010705401119000_2024.12.18.629250v1.124","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-2-r14"},{"key":"2025010705401119000_2024.12.18.629250v1.125","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"2025010705401119000_2024.12.18.629250v1.126","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELS.2015.12.004"},{"key":"2025010705401119000_2024.12.18.629250v1.127","doi-asserted-by":"crossref","unstructured":"B. Li , C. N. Dewey , RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12, 323 (2011).","DOI":"10.1186\/1471-2105-12-323"},{"key":"2025010705401119000_2024.12.18.629250v1.128","unstructured":"H. Pag\u00e8s , P. Aboyoun , R. Gentleman , S. DebRoy , Biostrings: Efficient manipulation of biological strings. R package version 2.74.0 (2024) https:\/\/bioconductor.org\/packages\/Biostrings."},{"key":"2025010705401119000_2024.12.18.629250v1.129","doi-asserted-by":"publisher","DOI":"10.1038\/nm0302-253"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.12.18.629250","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:48:19Z","timestamp":1768463299000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.12.18.629250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,2]]},"references-count":129,"URL":"https:\/\/doi.org\/10.1101\/2024.12.18.629250","relation":{},"subject":[],"published":{"date-parts":[[2025,1,2]]},"subtype":"preprint"}}