Five Recombinant Simian Immunodeficiency Virus Pseudotypes Lead to Exclusive Transduction of Retinal Pigmented Epithelium in Rat
Open accessAbstract
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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- 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
- hybrid
- doi.org
- Licence
- 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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