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Human Genetics

, Volume 135, Issue 9, pp 1059–1070 | Cite as

TALEN gene editing takes aim on HIV

  • Ronald Benjamin
  • Bradford K. Berges
  • Antonio Solis-Leal
  • Omoyemwen Igbinedion
  • Christy L. Strong
  • Martin R. Schiller
Review
Part of the following topical collections:
  1. Genome Editing

Abstract

Transcription activator-like effector nucleases (TALENs) are one of several types of programmable, engineered nucleases that bind and cleave specific DNA sequences. Cellular machinery repairs the cleaved DNA by introducing indels. In this review, we emphasize the potential, explore progress, and identify challenges in using TALENs as a therapeutic tool to treat HIV infection. TALENs have less off-target editing and can be more effective at tolerating HIV escape mutations than CRISPR/Cas-9. Scientists have explored TALEN-mediated editing of host genes such as viral entry receptors (CCR5 and CXCR4) and a protein involved in proviral integration (LEDGF/p75). Viral targets include the proviral DNA, particularly focused on the long terminal repeats. Major challenges with translating gene therapy from bench to bedside are improving cleavage efficiency and delivery, while minimizing off-target editing, cytotoxicity, and immunogenicity. However, rapid improvements in TALEN technology are enhancing cleavage efficiency and specificity. Therapeutic testing in animal models of HIV infection will help determine whether TALENs are a viable HIV treatment therapy. TALENs or other engineered nucleases could shift the therapeutic paradigm from life-long antiretroviral therapy toward eradication of HIV infection.

Keywords

Long Terminal Repeat Gene Editing Editing Efficiency TALEN Pair Packaging Capacity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Grants from the National Institutes of Health (R56 AI109156) and the Nevada Governors Office of Economic Development supported this work.

Compliance with ethical standards

Conflict of interest

Martin R. Schiller and Christy L. Strong have a patent pending for using TALENs to treat HIV, and thus have a potential conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Ronald Benjamin
    • 1
  • Bradford K. Berges
    • 2
  • Antonio Solis-Leal
    • 2
  • Omoyemwen Igbinedion
    • 1
  • Christy L. Strong
    • 1
  • Martin R. Schiller
    • 1
  1. 1.Nevada Institute of Personalized Medicine and School of Life SciencesUniversity of NevadaLas VegasUSA
  2. 2.Department of Microbiology and Molecular BiologyBrigham Young UniversityProvoUSA

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