Genome editing strategies: potential tools for eradicating HIV-1/AIDS

J Neurovirol. 2015 Jun;21(3):310-21. doi: 10.1007/s13365-014-0308-9. Epub 2015 Feb 26.


Current therapy for controlling human immunodeficiency virus (HIV-1) infection and preventing acquired immunodeficiency syndrome (AIDS) progression has profoundly decreased viral replication in cells susceptible to HIV-1 infection, but it does not eliminate the low level of viral replication in latently infected cells, which contain integrated copies of HIV-1 proviral DNA. There is an urgent need for the development of HIV-1 genome eradication strategies that will lead to a permanent or "sterile" cure of HIV-1/AIDS. In the past few years, novel nuclease-initiated genome editing tools have been developing rapidly, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR/Cas9 system. These surgical knives, which can excise any genome, provide a great opportunity to eradicate the HIV-1 genome by targeting highly conserved regions of the HIV-1 long terminal repeats or essential viral genes. Given the time consuming and costly engineering of target-specific ZFNs and TALENs, the RNA-guided endonuclease Cas9 technology has emerged as a simpler and more versatile technology to allow permanent removal of integrated HIV-1 proviral DNA in eukaryotic cells, and hopefully animal models or human patients. The major unmet challenges of this approach at present include inefficient nuclease gene delivery, potential off-target cleavage, and cell-specific genome targeting. Nanoparticle or lentivirus-mediated delivery of next generation Cas9 technologies including nickase or RNA-guided FokI nuclease (RFN) will further improve the potential for genome editing to become a promising approach for curing HIV-1/AIDS.

Publication types

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

MeSH terms

  • Acquired Immunodeficiency Syndrome / therapy*
  • Animals
  • Anti-Retroviral Agents / pharmacology*
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • Genetic Therapy / methods
  • Genome, Viral
  • HIV-1 / genetics*
  • Humans
  • Molecular Targeted Therapy / methods*
  • RNA, Viral / drug effects
  • Ribonucleases / pharmacology*


  • Anti-Retroviral Agents
  • RNA, Viral
  • Ribonucleases