Cited by 222Virus-based gene therapy researchRNA Interference and Gene DeliveryCRISPR and Genetic Engineering

Integration-deficient Lentiviral Vectors: A Slow Coming of Age

Open access
Wanisch, Klaus, Yáñez-Muñoz, Rafael J·2009·Molecular Therapy

Abstract

Lentiviral vectors are very efficient at transducing dividing and quiescent cells, which makes them highly useful tools for genetic analysis and gene therapy. Traditionally this efficiency was considered dependent on provirus integration in the host cell genome; however, recent results have challenged this view. So called integration-deficient lentiviral vectors (IDLVs) can be produced through the use of integrase mutations that specifically prevent proviral integration, resulting in the generation of increased levels of circular vector episomes in transduced cells. These lentiviral episomes lack replication signals and are gradually lost by dilution in dividing cells, but are stable in quiescent cells. Compared to integrating lentivectors, IDLVs have a greatly reduced risk of causing insertional mutagenesis and a lower risk of generating replication-competent recombinants (RCRs). IDLVs can mediate transient gene expression in proliferating cells, stable expression in nondividing cells in vitro and in vivo, specific immune responses, RNA interference, homologous recombination (gene repair, knock-in, and knock-out), site-specific recombination, and transposition. IDLVs can be converted into replicating episomes, suggesting that if a clinically applicable system can be developed they would also become highly appropriate for stable transduction of proliferating tissues in therapeutic applications.

Integrity signals

Registry

Crossref · 10.1038/mt.2009.122

Cites

151 of 151 references verified0 citation errors · 0 not checkable

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  • NILVs are still the best option for quiescent cells.

    “Thus, NILVs are still the best option for quiescent cells, as critically summarised in one review paper [75].”
  • Different mutation sites of the integrase plasmid resulted in different gene expression levels.

    “This approach could help to increase the episomal gene expression, as reported in a previous study where different mutation sites of the integrase plasmid resulted in different gene expression levels [75].”

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Authors
Wanisch, K., & Yáñez-Muñoz, R. J.
Affiliations
University of London (GB)
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2009-08
Volume
17
Issue
8
Pages
1316-1332
ISSN
1525-0016 (ISSN-L)
OpenAlex
W1976244438
Cited by
222
References
152
Citations by year
2026: 6 · 2025: 7 · 2024: 10 · 2023: 12 · 2022: 12 · 2021: 15 · 2020: 4 · 2019: 8 · 2018: 10 · 2017: 13 · 2016: 14 · 2015: 13 · 2014: 22 · 2013: 19 · 2012: 18
FWCI
1.76
Type
journal article
Language
en
Open access
Locations
  • Molecular Therapy (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Keywords
integrase mutations, proviral integration, insertional mutagenesis, quiescent cells, transient expression, stable transduction, homologous recombination, site-specific recombination, transposition, gene therapy
MeSH terms
Animals, Genetic Vectors, Humans, Mutation, Transduction, Genetic, Lentivirus, Integrases

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