Cited by 79Virus-based gene therapy researchRetinal Development and DisordersRNA Interference and Gene Delivery

Five Recombinant Simian Immunodeficiency Virus Pseudotypes Lead to Exclusive Transduction of Retinal Pigmented Epithelium in Rat

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Duisit, Ghislaine, Conrath, Hervé, Saleun, Sylvie, Folliot, Sebastien, Provost, Nathalie, Cosset, François-Loı¨c, Sandrin, Virginie, Moullier, Philippe +1 more·2002·Molecular Therapy

Abstract

The purpose of our study was to evaluate lentiviral vector-mediated rat retinal transduction using simian immunodeficiency virus (SIV) pseudotyped with envelope proteins from vesicular stomatitis virus G glycoprotein (VSV-G), Mokola virus G protein (MK-G), amphotropic murine leukemia virus envelope (4070A-Env), influenza A virus hemagglutinin (HA), lymphocytic choriomeningitis virus G protein (LCMV-G), and RD114 retrovirus envelope (RD114-Env). The six pseudotyped lentivirus vectors carried CMV-driven green fluorescent protein (GFP) or beta-galactosidase (beta-gal) reporter genes. Intravitreal and subretinal injections of each pseudotyped recombinant SIV were performed in cohorts of Wistar rats. Our results showed that no transgene expression was detected after intravitreal injection of each pseudotyped SIV vector. Also, no transduction could be detected following subretinal injection of RD114 pseudotyped SIV vectors. However, selective transduction of retinal pigment epithelium (RPE) cells was repeatedly obtained after subretinal delivery of VSV-G, MK-G, 4070A-Env, HA, and LCMV-G pseudotyped SIV. GFP expression was maximum as soon as 4 days postadministration for VSV-G, MK-G, 4070A-Env, and HA pseudotypes, with no evidence of pseudotransduction for VSV-G. Maximum transgene expression was observed 3 weeks postinjection for LCMV-6. Importantly, HA and VSV-G pseudotyped SIV lead to such a high level of transgene expression that GFP-related toxicity occurred. Therefore, when a high level of GFP synthesis is achieved, replacement of enhanced GFP (egfp, Aequorea victoria) by a low-toxicity GFP (Renilla reniformis) cDNA is necessary to allow long-term expression.

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Crossref · 10.1006/mthe.2002.0690

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Authors
Duisit, G., Conrath, H., Saleun, S., Folliot, S., Provost, N., Cosset, F.-L., Sandrin, V., Moullier, P., & Rolling, F.
Affiliations
  • Centre Hospitalier Universitaire de Nantes (FR)
  • Inserm (FR)
Corresponding author
Rolling, Fabienne
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2002-10
Volume
6
Issue
4
Pages
446-454
ISSN
1525-0016 (ISSN-L)
OpenAlex
W2316262719
Cited by
79
References
47
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2018: 1 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 4
FWCI
4.76
Type
journal article
Language
en
Open access
Locations
  • Molecular Therapy (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
simian immunodeficiency virus, lentiviral vectors, retinal pigment epithelium, retinal transduction, vesicular stomatitis virus glycoprotein, influenza A hemagglutinin, subretinal injection, intravitreal injection, transgene expression
MeSH terms
Animals, Genetic Vectors, Pigment Epithelium of Eye, Recombination, Genetic, Transduction, Genetic, Simian Immunodeficiency Virus, Rats

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