RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection

Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13157-62. doi: 10.1073/pnas.1410785111. Epub 2014 Aug 25.

Abstract

Latent viral infection is a persistent cause of human disease. Although standard antiviral therapies can suppress active viral replication, no existing treatment can effectively eradicate latent infection and therefore a cure is lacking for many prevalent viral diseases. The prokaryotic immune system clustered regularly interspaced short palindromic repeat (CRISPR)/Cas evolved as a natural response to phage infections, and we demonstrate here that the CRISPR/Cas9 system can be adapted for antiviral treatment in human cells by specifically targeting the genomes of latent viral infections. Patient-derived cells from a Burkitt's lymphoma with latent Epstein-Barr virus infection showed dramatic proliferation arrest and a concomitant decrease in viral load after exposure to a CRISPR/Cas9 vector targeted to the viral genome.

Keywords: genome editing; herpes virus; latency.

Publication types

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

MeSH terms

  • Base Sequence
  • CRISPR-Cas Systems / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics
  • Endonucleases / therapeutic use*
  • Epstein-Barr Virus Infections / drug therapy*
  • Epstein-Barr Virus Infections / pathology
  • Epstein-Barr Virus Infections / virology
  • Genome, Viral / genetics
  • Herpesvirus 4, Human / genetics
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • RNA Editing / genetics
  • RNA, Guide, CRISPR-Cas Systems / metabolism*
  • Sequence Deletion

Substances

  • RNA, Guide, CRISPR-Cas Systems
  • Endonucleases