Design and potential of non-integrating lentiviral vectors

Aaron Shaw, Kenneth Cornetta

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14-35
Number of pages22
JournalBiomedicines
Volume2
Issue number1
DOIs
StatePublished - Mar 1 2014

Fingerprint

Hematopoietic System
Integrases
Terminal Repeat Sequences
Insertional Mutagenesis
Genetic Therapy
Vaccination
Clinical Trials
Safety
Genes
Growth
Gene therapy
Cell growth
Neoplasms
Therapeutics
Cellular Reprogramming

Keywords

  • Episome
  • HIV
  • Integrase
  • Lentiviral
  • Non-integrating

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Design and potential of non-integrating lentiviral vectors. / Shaw, Aaron; Cornetta, Kenneth.

In: Biomedicines, Vol. 2, No. 1, 01.03.2014, p. 14-35.

Research output: Contribution to journalReview article

@article{6ae05e301cf14700b1422294e5898655,
title = "Design and potential of non-integrating lentiviral vectors",
abstract = "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.",
keywords = "Episome, HIV, Integrase, Lentiviral, Non-integrating",
author = "Aaron Shaw and Kenneth Cornetta",
year = "2014",
month = "3",
day = "1",
doi = "10.3390/biomedicines2010014",
language = "English (US)",
volume = "2",
pages = "14--35",
journal = "Biomedicines",
issn = "2227-9059",
publisher = "MDPI AG",
number = "1",

}

TY - JOUR

T1 - Design and potential of non-integrating lentiviral vectors

AU - Shaw, Aaron

AU - Cornetta, Kenneth

PY - 2014/3/1

Y1 - 2014/3/1

N2 - 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.

AB - 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.

KW - Episome

KW - HIV

KW - Integrase

KW - Lentiviral

KW - Non-integrating

UR - http://www.scopus.com/inward/record.url?scp=84930613490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930613490&partnerID=8YFLogxK

U2 - 10.3390/biomedicines2010014

DO - 10.3390/biomedicines2010014

M3 - Review article

AN - SCOPUS:84930613490

VL - 2

SP - 14

EP - 35

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 1

ER -