Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector.

Naldini, L; Blömer, U; Gage, F H; Trono, D; Verma, I M

doi:10.1073/pnas.93.21.11382

Cited by 1,499Virus-based gene therapy researchRNA Interference and Gene DeliveryBarrier Structure and Function Studies

Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector.

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Naldini, L, Blömer, U, Gage, F H, Trono, D, Verma, I M·1996·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.93.21.11382PMC PMC38066

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Abstract

We describe the construction of a safe, replication-defective and efficient lentiviral vector suitable for in vivo gene delivery. The reverse transcription of the vector was found to be a rate-limiting step; therefore, promoting the reaction inside the vector particles before delivery significantly enhanced the efficiency of gene transfer. After injection into the brain of adult rats, sustained long-term expression of the transgene was obtained in the absence of detectable pathology. A high proportion of the neurons in the areas surrounding the injection sites of the vector expressed the transduced beta-galactosidase gene. This pattern was invariant in animals sacrificed several months after a single administration of the vector. Transduction occurs by integration of the vector genome, as it was abolished by a single amino acid substitution in the catalytic site of the integrase protein incorporated in the vector. Development of clinically acceptable derivatives of the lentiviral vector may thus enable the sustained delivery of significant amounts of a therapeutic gene product in a wide variety of somatic tissues.

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Crossref · 10.1073/pnas.93.21.11382

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Authors: Naldini, L., Blömer, U., Gage, F. H., Trono, D., & Verma, I. M.
Affiliations: Salk Institute for Biological Studies (US)
ORCID: Naldini, L
Gage, F H
Trono, D
Verma, I M
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1996-10-15
Volume: 93
Issue: 21
Pages: 11382-11388
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.93.21.11382
PMC: PMC38066
OpenAlex: W1981449360
Cited by: 1,499
References: 54
Citations by year: 2026: 9 · 2025: 18 · 2024: 11 · 2023: 16 · 2022: 34 · 2021: 55 · 2020: 36 · 2019: 25 · 2018: 32 · 2017: 40 · 2016: 34 · 2015: 40 · 2014: 56 · 2013: 71 · 2012: 88
FWCI: 17.79
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
Funders: American Cancer Society
American-Italian Cancer Foundation
Deutsche Forschungsgemeinschaft
National Institutes of Health (5r01ai037510-02, AG10435)
U.S. Public Health Service
National Institute on Aging (P01AG010435, AG 08514, AG10435)
National Institute of Allergy and Infectious Diseases (AI 37510)
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 › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: lentiviral vectors, in vivo gene delivery, transgene integration, reverse transcription, sustained transgene expression, replication-defective virus, beta-galactosidase expression, neuronal transduction, vector safety
MeSH terms: Animals, beta-Galactosidase, Brain, Cell Line, Cytomegalovirus, Genetic Vectors, Humans, Kidney, Lac Operon, Neurons, Safety, Genes, gag, Genes, pol, Lentivirus, Virus Integration, Genes, Reporter, Gene Transfer Techniques, Animals, Genetically Modified, Rats

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Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector.

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