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Open AccessReview

Design and Potential of Non-Integrating Lentiviral Vectors

by Aaron Shaw 1 and Kenneth Cornetta 1,2,3,*
1
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
*
Author to whom correspondence should be addressed.
Biomedicines 2014, 2(1), 14-35; https://doi.org/10.3390/biomedicines2010014
Received: 7 November 2013 / Revised: 22 January 2014 / Accepted: 23 January 2014 / Published: 27 January 2014
(This article belongs to the Special Issue Feature Papers)
Lentiviral vectors have demonstrated promising results in clinical trials that target cells of the hematopoietic system. For these applications, they are the vectors of choice since they provide stable integration into cells that will undergo extensive expansion in vivo. Unfortunately, integration can have unintended consequences including dysregulated cell growth. Therefore, lentiviral vectors that do not integrate are predicted to have a safer profile compared to integrating vectors and should be considered for applications where transient expression is required or for sustained episomal expression such as in quiescent cells. In this review, the system for generating lentiviral vectors will be described and used to illustrate how alterations in the viral integrase or vector Long Terminal Repeats have been used to generate vectors that lack the ability to integrate. In addition to their safety advantages, these non-integrating lentiviral vectors can be used when persistent expression would have adverse consequences. Vectors are currently in development for use in vaccinations, cancer therapy, site-directed gene insertions, gene disruption strategies, and cell reprogramming. Preclinical work will be described that illustrates the potential of this unique vector system in human gene therapy. View Full-Text
Keywords: HIV; non-integrating; episome; lentiviral; integrase HIV; non-integrating; episome; lentiviral; integrase
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Shaw, A.; Cornetta, K. Design and Potential of Non-Integrating Lentiviral Vectors. Biomedicines 2014, 2, 14-35.

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