MicroRNA-based recombinant AAV vector assembly improves efficiency of suicide gene transfer in a murine model of lymphoma.

ABSTRACT: Recent success in clinical trials with recombinant Adeno-associated virus (AAV)-based gene therapy has redirected efforts in optimizing AAV assembly and production, to improve its potency. We reasoned that inclusion of a small RNA during vector assembly, which specifically alters the phosphorylation status of the packaging cells may be beneficial. We thus employed microRNAs (miR-431, miR-636) identified by their ability to bind AAV genome and also dysregulate Mitogen-activated protein kinase (MAPK) signaling during vector production, by a global transcriptome study in producer cells. A modified vector assembly protocol incorporating a plasmid encoding these microRNAs was developed. AAV2 vectors packaged in the presence of microRNA demonstrated an improved gene transfer potency by 3.7-fold,

SUBMITTER: Khan N 

PROVIDER: S-EPMC7196056 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature