Stem cell-derived clade F AAVs mediate high-efficiency homologous recombination-based genome editing.

ABSTRACT: The precise correction of genetic mutations at the nucleotide level is an attractive permanent therapeutic strategy for human disease. However, despite significant progress, challenges to efficient and accurate genome editing persist. Here, we report a genome editing platform based upon a class of hematopoietic stem cell (HSC)-derived clade F adeno-associated virus (AAV), which does not require prior nuclease-mediated DNA breaks and functions exclusively through BRCA2-dependent homologous recombination. Genome editing is guided by complementary homology arms and is highly accurate and seamless, with no evidence of on-target mutations, including insertion/deletions or inclusion of AAV inverted terminal repeats. Efficient genome editing was demonstrated at different loci within the human gen

SUBMITTER: Smith LJ 

PROVIDER: S-EPMC6077703 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature