{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:49:03Z","timestamp":1792144143368,"version":"4.4.0"},"reference-count":0,"publisher":"Armed Forces Medical Services","issue":"4","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Saudi Medical Journal"],"abstract":"<jats:p>Gene therapy targets diabetes pathophysiology rather than symptoms, yet clinical translation is slower than preclinical success. This review synthesizes 143 registered trials (ClinicalTrials.gov, 2010-2025) identifying systematic implementation barriers. Despite &gt;15 years of development, 83% of trials remain in Phase I-II. Only zimislecel achieved Phase III outcomes (83% insulin independence at 12 months, n=12, requiring immunosuppression). VM202 for diabetic neuropathy failed Phase III despite positive extension results. Three systematic barriers emerged: (1) human transduction efficiency is 6-8.7-fold lower than preclinical models; (2) pre-existing immunity excludes 58-78% of candidates; (3) manufacturing capacity serves &lt;2.5% of target population (40-400 years to treat at maximum capacity). These constraints explain why ex vivo cell therapies advanced to efficacy trials while in vivo gene delivery remains in Phase I despite longer development timelines. Research priorities should emphasize non-viral delivery systems offering scalable manufacturing and universal hypoimmune donor cells to address access barriers.<\/jats:p>","DOI":"10.15537\/1658-3175.1061","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T14:48:16Z","timestamp":1774104496000},"page":"626-652","source":"Crossref","is-referenced-by-count":1,"title":["Translational Barriers to AAV and CRISPR Gene Therapy in Diabetes"],"prefix":"10.15537","volume":"47","author":[{"given":"Abdulrahman G.","family":"Alharbi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al Medina Al Munawara, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56029","published-online":{"date-parts":[[2026,3,20]]},"container-title":["Saudi Medical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/smj.researchcommons.org\/cgi\/viewcontent.cgi?article=1061&amp;context=journal","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:27:54Z","timestamp":1792142874000},"score":1,"resource":{"primary":{"URL":"https:\/\/smj.researchcommons.org\/journal\/vol47\/iss4\/5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":0,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,3,20]]}},"URL":"https:\/\/doi.org\/10.15537\/1658-3175.1061","relation":{},"ISSN":["1658-3175"],"issn-type":[{"value":"1658-3175","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,20]]}}}