biostudies-literatureChai SNIDDK NIH HHS789-800https://www.ebi.ac.uk/biostudies/studies/S-EPMC9419973biostudies-literatureUnknown33(15-16)Diabetes mellitus, caused by loss or dysfunction of the insulin-producing beta cells of the pancreas, is a promising target for recombinant adeno-associated virus (rAAV)-mediated gene therapy. To target potential therapeutic payloads specifically to beta cells, a cell type-specific expression control element is needed. In this study, we tested a series of rAAV vectors designed to express transgenes specifically in human beta cells using the islet-tropic rAAV-KP1 capsid. A small promoter, consisting of only 84 bp of the insulin core promoter was not beta cell-specific in AAV, but highly active in multiple cell types, including tissues outside the pancreas. A larger 363 bp fragment of the insulin promoter (INS) also lacked beta cell specificity. However, beta cell-specific expression was achHuman gene therapyDevelopment of a Beta Cell-Specific Expression Control Element for Recombinant Adeno-Associated Virus.PMC9419973U01 DK123608Ackermann AMPosey JGrompe MKaestner KHHebrok MKim YWakefield LChai SGalivo FDorrell CfalseDevelopment of a Beta Cell-Specific Expression Control Element for Recombinant Adeno-Associated Virus.Diabetes mellitus, caused by loss or dysfunction of the insulin-producing beta cells of the pancreas, is a promising target for recombinant adeno-associated virus (rAAV)-mediated gene therapy. To target potential therapeutic payloads specifically to beta cells, a cell type-specific expression control element is needed. In this study, we tested a series of rAAV vectors designed to express transgenes specifically in human beta cells using the islet-tropic rAAV-KP1 capsid. A small promoter, consisting of only 84 bp of the insulin core promoter was not beta cell-specific in AAV, but highly active in multiple cell types, including tissues outside the pancreas. A larger 363 bp fragment of the insulin promoter (INS) also lacked beta cell specificity. However, beta cell-specific expression was ach2022-01-01T00:00:00Z2022 Aug2025-04-04T20:33:06.384Z2025-04-04T20:33:06.384ZS-EPMC94199733529768010.1089/hum.2021.219