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PMID: 10438872 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer.

Journal of virology ·Vol. 73 ·No. 9 ·1999-09-00 ·Pages 7812-6

Takahashi M, Miyoshi H, Verma IM, Gage FH

Abstract

Retinitis pigmentosa (RP) is the most common inherited retinal disease, in which photoreceptor cells degenerate, leading to blindness. Mutations in the rod photoreceptor cGMP phosphodiesterase beta subunit (PDEbeta) gene are found in patients with autosomal recessive RP as well as in the rd mouse. We have recently shown that lentivirus vectors based on human immunodeficiency virus (HIV) type 1 achieve stable and efficient gene transfer into retinal cells. In this study, we evaluated the potential of HIV vector-mediated gene therapy for RP in the rd mouse. HIV vectors containing a gene encoding a hemagglutinin (HA)-tagged PDEbeta were injected into the subretinal spaces of newborn rd mouse eyes. One to three rows of photoreceptor nuclei were observed in the eyes for at least 24 weeks postinjection, whereas no photoreceptor cells remained in the eyes of control animals at 6 weeks postinjection. Expression of HA-tagged PDEbeta in the rescued photoreceptor cells was confirmed by two-color confocal immunofluorescence analysis using anti-HA and anti-opsin antibodies. HIV vector-mediated gene therapy appears to be a promising means for the treatment of recessive forms of inherited retinal degeneration.

MeSH Terms
3',5'-Cyclic-GMP Phosphodiesterases/genetics Animals Cattle Cyclic Nucleotide Phosphodiesterases, Type 6 Gene Transfer Techniques Genetic Therapy Genetic Vectors HIV-1 Humans Mice Mice, Inbred C3H Phosphoric Diester Hydrolases Retinal Rod Photoreceptor Cells Retinitis Pigmentosa/therapy
Chemicals
Phosphoric Diester Hydrolases 3',5'-Cyclic-GMP Phosphodiesterases Cyclic Nucleotide Phosphodiesterases, Type 6 PDE6B protein, human Pde6b protein, mouse
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Takahashi M
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Miyoshi H
Verma I M
Gage F H
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.73.9.7812-7816.1999
Published
1999-09-00
Pages
7812-6
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC104309
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.73.9.7812-7816.1999 PMC Full Text View journal details
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