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

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Integration-deficient Lentiviral Vectors: A Slow Coming of Age

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

DOI 10.1038/mt.2009.122PMC PMC2835240

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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.

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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)
DOI: 10.1038/mt.2009.122
PMC: PMC2835240
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: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 2624 d)
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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Integration-deficient Lentiviral Vectors: A Slow Coming of Age

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