CRISPR-Cas9 Mediated Exonic Disruption for HIV-1 Elimination.

ABSTRACT:

Background

A barrier to HIV-1 cure rests in the persistence of proviral DNA in infected CD4+ leukocytes. The high HIV-1 mutation rate leads to viral diversity, immune evasion, and consequent antiretroviral drug resistance. While CRISPR-spCas9 can eliminate latent proviral DNA, its efficacy is limited by HIV strain diversity and precision target cell delivery.

Methods

A library of guide RNAs (gRNAs) designed to disrupt five HIV-1 exons (tat_1-2/rev_1-2/gp41) was constructed. The gRNAs were derived from a conseensus sequence of the transcriptional regulator tat from 4004 HIV-1 strains. Efficacy was affirmed by gRNA cell entry through transfection, electroporation, or by lentivirus or lipid nanoparticle (LNP) delivery. Treated cells were evaluated for viral

SUBMITTER: Herskovitz J 

PROVIDER: S-EPMC8633974 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature