HIV-1 sequences in lentiviral vector genomes can be substantially reduced without compromising transduction efficiency.

ABSTRACT: Many lentiviral vectors used for gene therapy are derived from HIV-1. An optimal vector genome would include only the viral sequences required for transduction efficiency and gene expression to minimize the amount of foreign sequence inserted into a patient's genome. However, it remains unclear whether all of the HIV-1 sequence in vector genomes is essential. To determine which viral sequences are required, we performed a systematic deletion analysis, which showed that most of the gag region and over 50% of the env region could be deleted. Because the splicing profile for lentiviral vectors is poorly characterized, we used long-read sequencing to determine canonical and cryptic splice site usage. Deleting specific regions of env sequence reduced the number of splicing events per transcript

SUBMITTER: Sertkaya H 

PROVIDER: S-EPMC8187449 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature