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Biomedicines 2016, 4(1), 4; doi:10.3390/biomedicines4010004

Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy

1
School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA
2
Pharmaceutical Sciences, College of Pharmacy, Washington State University Spokane, Spokane, WA 99202, USA
*
Author to whom correspondence should be addressed.
Academic Editor: N. Manjunath
Received: 9 October 2015 / Revised: 26 January 2016 / Accepted: 28 January 2016 / Published: 2 February 2016
(This article belongs to the Special Issue Gene Therapy Strategies for HIV/AIDS)
View Full-Text   |   Download PDF [1196 KB, uploaded 2 February 2016]   |  

Abstract

Retroviral vector gene therapy is a promising approach to treating HIV-1. However, integrated vectors are mutagens with the potential to dysregulate nearby genes and cause severe adverse side effects. Leukemia has already been a documented severe adverse event in gene therapy clinical trials for the treatment of primary immunodeficiencies. These side effects will need to be reduced or avoided if retroviral vectors are to be used clinically for HIV-1 treatment. The addition of chromatin insulators to retroviral vectors is a potential strategy for reducing adverse side effects. Insulators have already been effectively used in retroviral vectors to reduce genotoxicity in pre-clinical studies. Here, we will review how insulators function, genotoxicity in gene therapy clinical trials, the design of insulated retroviral vectors, promising results from insulated retroviral vector studies, and considerations for the development of insulated retroviral treatment vectors for HIV-1 gene therapy. View Full-Text
Keywords: retroviral vector; insulator; genotoxicity; insertional mutagenesis; anti-HIV; gene therapy; clinical trial retroviral vector; insulator; genotoxicity; insertional mutagenesis; anti-HIV; gene therapy; clinical trial
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Browning, D.L.; Trobridge, G.D. Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy. Biomedicines 2016, 4, 4.

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