Highly efficient <i>in vivo</i> hematopoietic stem cell transduction using an optimized self-complementary adeno-associated virus.

ABSTRACT: In vivo gene therapy targeting hematopoietic stem cells (HSCs) holds significant therapeutic potential for treating hematological diseases. This study uses adeno-associated virus serotype 6 (AAV6) vectors and Cre recombination to systematically optimize the parameters for effective in vivo HSC transduction. We evaluated various genetic architectures and delivery methods of AAV6, establishing an optimized protocol that achieved functional recombination in more than two-thirds of immunophenotypic HSCs. Our findings highlight that second-strand synthesis is a critical limiting factor for transgene expression in HSCs, leading to significant under-detection of HSC transduction with single-stranded AAV6 vectors. We also demonstrate that HSCs in the bone marrow (BM) are readily acce

SUBMITTER: Charlesworth CT 

PROVIDER: S-EPMC11930595 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature