{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:29:59Z","timestamp":1777660199512,"version":"3.51.4"},"reference-count":39,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Incurable hereditary diseases such as Duchenne muscular dystrophy (DMD), Huntington\u2019s disease (HD), and myotonic dystrophy type 1 (DM1) fall into the nucleotide repeat expansion disorder (NRED) category. The discovery of CRISPR-Cas genome editing has paved the way toward hopeful strategies for accurate DNA-level repair. This systematic review presents preclinical data on the efficacy, molecular effects, and limitations of CRISPR-based treatments for NREDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, systematic PubMed, Scopus, and Embase searches up to June 2025 identified studies that evaluated CRISPR-Cas systems in human-derived\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      models of NREDs. Methodological Index for Non-Randomized Studies tool was used to score eligible studies by methodological quality. CRISPR platforms, delivery systems, gene targets, molecular endpoints, and functional rescue data were extracted and synthesized descriptively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Twenty-four out of 6510 records screened were included. They employed most of them to target specific DMD (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 9), HD (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 6), and DM1 (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 3) with patient-derived induced pluripotent stem cells or differentiated myogenic\/neuronal cells. Streptococcus pyogenes CRISPR-associated protein 9 as a nuclease was the most frequently used, although engineered Cas9 enzymes and dCas9 fusion proteins were also utilized to control transcription. Delivery was achieved through viral vectors (adeno-associated virus, lentivirus) and nonviral routes (plasmid, lipofection, electroporation). Uniform genomic editing, transcript rescue, and protein restoration were seen in CRISPR-mediated editing studies, and functional restoration was demonstrated for splicing correction and dystrophin restoration. Methodological flaws such as the absence of blinding, failure to follow up, and lack of full reporting of off-target effects limited robustness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      CRISPR-Cas systems exhibit reproducible molecular and functional correction in NRED models with their translational potential. Methodological strength, whole safety profiling, and\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      verification remain a necessity, however, before clinical translation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19450265261434900","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:21:55Z","timestamp":1773724915000},"page":"71-80","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["CRISPR Gene Editing for Nucleotide Repeat Expansion Disorders: A Systematic Review of Preclinical and Clinical Evidence"],"prefix":"10.1177","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6361-6586","authenticated-orcid":false,"given":"Husna Irfan","family":"Thalib","sequence":"first","affiliation":[{"name":"General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sariya","family":"Khan","sequence":"additional","affiliation":[{"name":"General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayesha","family":"Hanin Shaikh","sequence":"additional","affiliation":[{"name":"General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenanah Maher","family":"Alawi","sequence":"additional","affiliation":[{"name":"General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra Hussein","family":"Alabdrabalrasol","sequence":"additional","affiliation":[{"name":"General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayeeda","family":"Mehveen","sequence":"additional","affiliation":[{"name":"Bachelors of Genetics, St. Ann\u2019s College for Women, Hyderabad, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyma","family":"Haidar","sequence":"additional","affiliation":[{"name":"General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma","family":"ElSayed Hassan","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Kasr Alainy, Faculty of Medicine, Cairo University, Giza, Egypt."},{"name":"Department of Physiology, General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noor Ahmad","family":"Shaik","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.80229"},{"key":"e_1_3_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2024.102247"},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252111794"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0212198"},{"key":"e_1_3_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-60192-2_9"},{"key":"e_1_3_5_7_1","doi-asserted-by":"publisher","DOI":"10.37349\/ent.2024.00095"},{"key":"e_1_3_5_8_1","unstructured":"Cochrane Methods. 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