Designing broad-spectrum anti-HIV-1 gRNAs to target patient-derived variants

Sci Rep. 2017 Oct 31;7(1):14413. doi: 10.1038/s41598-017-12612-z.

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated protein 9 (Cas9), including specific guide RNAs (gRNAs), can excise integrated human immunodeficiency virus type 1 (HIV-1) provirus from host chromosomes. To date, anti-HIV-1 gRNAs have been designed to account for off-target activity, however, they seldom account for genetic variation in the HIV-1 genome within and between patients, which will be crucial for therapeutic application of this technology. This analysis tests the ability of published anti-HIV-1 gRNAs to cleave publicly available patient-derived HIV-1 sequences to inform gRNA design and provides basic computational tools to researchers in the field.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CRISPR-Cas Systems*
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • Computational Biology
  • Computer Simulation
  • Gene Editing
  • Genome, Viral
  • HIV Infections / genetics
  • HIV-1 / genetics*
  • Humans
  • RNA, Guide, CRISPR-Cas Systems*

Substances

  • RNA, Guide, CRISPR-Cas Systems