Year: 2019
Type: article
Abstract: While gene transfer using recombinant adeno-associated viral (rAAV) vectors has shown success in some clinical trials, there remain many tissues that are not well transduced. Because of the recent success in reprogramming islet-derived cells into functional β cells in animal models, we constructed 2 highly complex barcoded replication competent capsid shuffled libraries and selected for high-transducing variants on primary human islets. We describe the generation of a chimeric AAV capsid (AAV-KP1) that facilitates transduction of primary human islet cells and human embryonic stem cell-derived β cells with up to 10-fold higher efficiency compared with previously studied best-in-class AAV vectors. Remarkably, this chimeric capsid also enabled transduction of both mouse and human hepatocytes at very high levels in a humanized chimeric mouse model, thus providing a versatile vector that has the potential to be used in both preclinical testing and human clinical trials for liver-based diseases and diabetes.
Source: JCI Insight
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: In vivo targeting of diabetes-relevant human cell types with rAAV vectors, G2366920275, G2878360865, G2986059996, G368404675, G3885216397, G4052331345, G5520316217, G6607237905, Nikon A1Rsi resonant spectral confocal microscope, G844559411, G9000051547, G9000247158, Integrated Islet Distribution Program (U24) - 2021, Stanford Diabetes Research Center, AAV capsid engineering for enhancing gene transfer
OpenAlex ID: W2983325814