Differential effects of DNA double-strand break repair pathways on single-strand and self-complementary adeno-associated virus vector genomes.

ABSTRACT: The linear DNA genomes of recombinant adeno-associated virus (rAAV) gene delivery vectors are acted upon by multiple DNA repair and recombination pathways upon release into the host nucleus, resulting in circularization, concatemer formation, or chromosomal integration. We have compared the fates of single-strand rAAV (ssAAV) and self-complementary AAV (scAAV) genomes in cell lines deficient in each of three signaling factors, ATM, ATR, and DNA-PK(CS), orchestrating major DNA double-strand break (DSB) repair pathways. In cells deficient in ATM, transduction as scored by green fluorescent protein (GFP) expression is increased relative to that in wild-type (wt) cells by 2.6-fold for ssAAV and 6.6-fold for scAAV vectors, arguing against a mechanism related to second-strand synthesis. The augm

SUBMITTER: Cataldi MP 

PROVIDER: S-EPMC2918998 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature