{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T19:14:00Z","timestamp":1782760440048,"version":"3.54.5"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Introduction: Gene therapy has emerged as a promising frontier in the management of diabetes, offering innovative approaches to address both type 1 and type 2 diabetes. This narrative review examines the advancements in gene therapy applications, focusing on both animal and human studies, and includes a total of 11 studies in adherence to PRISMA guidelines. These studies utilize various viral vectors, such as adeno-associated virus (AAV) and lentivirus, to deliver genes that regulate insulin production and enhance angiogenesis. This review aims to synthesize recent advancements in gene therapy for both type 1 and type 2 diabetes and its complications, and to explore the evolving role of pharmacists in this emerging field. Methods: A comprehensive search was conducted to identify relevant studies on gene therapy for diabetes. Databases such as PubMed, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and Google Scholar were queried using keywords such as \u201cDiabetes\u201d, \u201cgene therapy\u201d, \u201cType 1 diabetes\u201d, and \u201cType 2 diabetes\u201d. Both animal and human studies were included to provide a broad perspective on the advancements in this field. Results: Animal model studies have shown promising results, including sustained insulin production, improved glucose homeostasis, and enhanced wound healing. Human studies, though fewer in number, have reported significant advancements. Patients with diabetic neuropathy treated with plasmid VEGF and recombinant adeno-associated virus (rAAV) showed improvements in neuropathic symptoms and glycemic control. Other studies involving intramuscular injections of VM202 and bicistronic VEGF165\/HGF plasmid have reported pain reduction, improved healing of ischemic lesions, and increased angiogenesis. Conclusions: Despite these encouraging results, limitations such as small sample sizes, short follow-up periods, and the necessity for more extensive clinical trials persist. Diabetes is a metabolic syndrome that requires the collaboration of a multidisciplinary team to assist in several aspects of implementing successful gene therapy. Several healthcare providers and policy makers may play a crucial role in patient education, counseling, and the management of gene therapy treatments.<\/jats:p>","DOI":"10.3390\/genes16010107","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T04:04:12Z","timestamp":1737345852000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Gene Therapy and Diabetes: A Narrative Review of Recent Advances and the Role of Multidisciplinary Healthcare Teams"],"prefix":"10.3390","volume":"16","author":[{"given":"Nadia","family":"Khartabil","sequence":"first","affiliation":[{"name":"School of Pharmacy, Center of Graduate Studies, West Coast University, 590 N Vermont Ave, Los Angeles, CA 90004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ani","family":"Avoundjian","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Center of Graduate Studies, West Coast University, 590 N Vermont Ave, Los Angeles, CA 90004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"ref_1","unstructured":"American Diabetes Association (2023). Statistics About Diabetes, American Diabetes Association."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.eprac.2022.08.002","article-title":"American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update","volume":"28","author":"Blonde","year":"2022","journal-title":"Endocr. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.2337\/diaclin.30.2.44","article-title":"The Ideal Diabetes Therapy: What Will It Look Like? How Close Are We?","volume":"30","author":"Rotenstein","year":"2012","journal-title":"Clin. Diabetes"},{"key":"ref_4","unstructured":"(2024, December 01). What Is Gene Therapy?, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/what-gene-therapy."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"120375","DOI":"10.1016\/j.lfs.2022.120375","article-title":"Gene therapy: Comprehensive overview and therapeutic applications","volume":"294","author":"Sayed","year":"2022","journal-title":"Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nrendo.2009.276","article-title":"Stem cell and gene therapies for diabetes mellitus","volume":"6","author":"Calne","year":"2010","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1615\/CritRevImmunol.v28.i4.30","article-title":"Gene therapy in type 1 diabetes","volume":"28","author":"Bagley","year":"2008","journal-title":"Crit. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2174\/1566523033347444","article-title":"Diabetes gene therapy: Potential and challenges","volume":"3","author":"Xu","year":"2003","journal-title":"Curr. Gene Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"eadi5377","DOI":"10.1126\/sciimmunol.adi5377","article-title":"Regulatory T cells shield muscle mitochondria from interferon-\u03b3-mediated damage to promote the beneficial effects of exercise","volume":"8","author":"Langston","year":"2023","journal-title":"Sci. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nrg2971","article-title":"State-of-the-art gene-based therapies: The road ahead","volume":"12","author":"Kay","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.2337\/db12-1113","article-title":"Treatment of Diabetes and Long-Term Survival After Insulin and Glucokinase Gene Therapy","volume":"62","author":"Callejas","year":"2013","journal-title":"Diabetes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1111\/jdi.13860","article-title":"Precision diabetes: Lessons learned from maturity-onset diabetes of the young (MODY)","volume":"13","author":"Tosur","year":"2022","journal-title":"J. Diabetes Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109076","DOI":"10.1016\/j.clim.2022.109076","article-title":"Effect of IL4 and IL10 on a human in vitro type 1 diabetes model","volume":"241","author":"Pfeiffer","year":"2022","journal-title":"Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2174\/1566524013363979","article-title":"Adeno-associated virus (AAV) as a vehicle for therapeutic gene delivery: Improvements in vector design and viral production enhance potential to prolong graft survival in pancreatic islet cell transplantation for the reversal of type 1 diabetes","volume":"1","author":"Kapturczak","year":"2001","journal-title":"Curr. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101209","DOI":"10.1016\/j.molmet.2021.101209","article-title":"RNA m6A reader IMP2\/IGF2BP2 promotes pancreatic \u03b2-cell proliferation and insulin secretion by enhancing PDX1 expression","volume":"48","author":"Zhao","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"4","author":"Moher","year":"2015","journal-title":"Syst. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan\u2014A web and mobile app for systematic reviews. Systematic Reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_18","first-page":"285","article-title":"The Mixed Methods Appraisal Tool (MMAT) version 2018 for information professionals and researchers","volume":"34","author":"Hong","year":"2018","journal-title":"Educ. Inf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.4103\/sja.SJA_559_18","article-title":"The CONSORT statement","volume":"13","author":"Cuschieri","year":"2019","journal-title":"Saudi J. Anaesth."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/nm867","article-title":"NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice","volume":"9","author":"Kojima","year":"2003","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/mt.2012.8","article-title":"Reversal of diabetes through gene therapy of diabetic rats by hepatic insulin expression via lentiviral transduction","volume":"20","author":"Elsner","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.2353\/ajpath.2006.051251","article-title":"Vascular endothelial growth factor-C accelerates diabetic wound healing","volume":"169","author":"Saaristo","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7964","DOI":"10.1073\/pnas.0405277102","article-title":"Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells","volume":"102","author":"Sapir","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","first-page":"37","article-title":"Insulin gene therapy for type 1 diabetes mellitus","volume":"13","author":"Handorf","year":"2015","journal-title":"Exp. Clin. Transplant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1007\/s11095-008-9539-x","article-title":"Glucose- and Metabolically Regulated Hepatic Insulin Gene Therapy for Diabetes","volume":"25","author":"Hsu","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s12265-020-10066-9","article-title":"Double VEGF\/HGF Gene Therapy in Critical Limb Ischemia Complicated by Diabetes Mellitus","volume":"14","author":"Antkiewicz","year":"2021","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1111\/cts.12977","article-title":"Gene therapy for diabetic peripheral neuropathy: A randomized, placebo-controlled phase III study of VM202, a plasmid DNA encoding human hepatocyte growth factor","volume":"14","author":"Kessler","year":"2021","journal-title":"Clin. Transl. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/ana.21675","article-title":"Vascular endothelial growth factor gene transfer for diabetic polyneuropathy: A randomized, double-blinded trial","volume":"65","author":"Ropper","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kupczy\u0144ska, D., Lubieniecki, P., Antkiewicz, M., Bar\u0107, J., Fr\u0105czkowska-Sioma, K., Dawiskiba, T., Dorobisz, T., Ma\u0142odobra-Mazur, M., Baczy\u0144ska, D., and Pa\u0144czak, K. (2023). Complementary Gene Therapy after Revascularization with the Saphenous Vein in Diabetic Foot Syndrome. Genes, 14.","DOI":"10.3390\/genes14101968"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/s41574-024-01030-7","article-title":"The promising potential of gene therapy for diabetes mellitus","volume":"20","author":"Bornstein","year":"2024","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.2337\/dci20-0022","article-title":"Precision Medicine in Diabetes: A Consensus Report From the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"43","author":"Chung","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1182\/hematology.2023000487","article-title":"Gene therapy for sickle cell disease","volume":"2023","author":"Leonard","year":"2023","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program."},{"key":"ref_33","unstructured":"MTPConnect (2024, August 14). Restoring Glucose Control in T1D Patients With Genetically Engineered GARV-AAV2-A20-Islet Cells\u2014A First in Human Safety And Efficacy Trial. Available online: https:\/\/www.mtpconnect.org.au\/Category?Action=View&Category_id=395."},{"key":"ref_34","first-page":"1441","article-title":"Pharmacogenomics and Personalized Medicine in Type 2 Diabetes Mellitus: Potential Implications for Clinical Practice","volume":"14","author":"Venkatachalapathy","year":"2021","journal-title":"Pharmgenomics Pers. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S2213-8587(23)00129-8","article-title":"Disparities in diabetes prevalence and management by race and ethnicity in the USA: Defining a path forward","volume":"11","author":"Hassan","year":"2023","journal-title":"Lancet Diabetes Endocrinol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/1\/107\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:32:03Z","timestamp":1759919523000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/1\/107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,20]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["genes16010107"],"URL":"https:\/\/doi.org\/10.3390\/genes16010107","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,20]]}}}