Modulation of AAV transduction and integration targeting by topoisomerase poisons.

ABSTRACT: Adeno-associated virus (AAV) is a widely used vehicle for gene delivery, lending interest to developing methods for enhancing AAV transduction and transgene expression. Here, we profile the function of several topoisomerase poisons, which are small molecules that stabilize topoisomerase enzymatic intermediates, where topoisomerase enzymes are covalently bound at chromosomal DNA breaks. As previously observed, we found that the topoisomerase poisons camptothecin (CPT), doxorubicin (DOX), and etoposide (ETO) increased AAV transduction in cultured cell models. DOX and ETO, small molecules that specifically inhibit type II topoisomerases and so stabilize double-strand breaks, were found to boost integration of AAV DNA into the host cell chromosome. Analysis of integration site distributions sh

SUBMITTER: Kasimsetty A 

PROVIDER: S-EPMC11607603 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature