Activity analysis of housekeeping promoters using self-inactivating lentiviral vector delivery into the mouse retina.

Details

Serval ID
serval:BIB_09B86DC7497E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Activity analysis of housekeeping promoters using self-inactivating lentiviral vector delivery into the mouse retina.
Journal
Gene Therapy
Author(s)
Kostic C., Chiodini F., Salmon P., Wiznerowicz M., Deglon N., Hornfeld D., Trono D., Aebischer P., Schorderet D.F., Munier F.L., Arsenijevic Y.
ISSN
0969-7128 (Print)
ISSN-L
0969-7128
Publication state
Published
Issued date
2003
Volume
10
Number
9
Pages
818-821
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
For most retinal degeneration disorders, no efficient treatment exists to preserve photoreceptors (PRs) and, consequently, to maintain vision. Gene transfer appears to be a promising approach to prevent PR loss. In order to design adequate vectors to target specific retinal cell types, we have analyzed the expression pattern of three different promoters (mouse phosphoglycerate kinase 1 (PGK), elongation factor-1 (EFS), rhodopsin (Rho)) in newborn and adult DBA/2 mice retinas using self-inactivating lentiviral vectors. At 7 days after intraocular injection and in optimal conditions, cell transduction was observed up to 1.5 mm from the injection site. PGK promoter expression was predominant in the retinal pigment epithelium (RPE), especially in adult mice, whereas the EFS promoter allowed a broad expression in the retina. Finally, as expected, the Rho promoter was specifically expressed in PRs. Differences in the cell types transduced and in transduction efficiency were observed between newborn and adult injected eyes emphasizing the importance of such basic studies for further gene therapy approaches as well as for understanding the transcriptional changes during retinal maturation. Thus, for future attempts to slow or rescue retinal degeneration by lentiviral delivery, PGK and EFS are more suitable to control the expression of a supporting secreted factor, PGK being mainly expressed in RPE and EFS in different cell types throughout the entire retina, whereas Rho should allow to specifically deliver the therapeutic gene to PRs.
Keywords
Animals, Animals, Newborn, Gene Expression, Genetic Therapy/methods, Genetic Vectors/administration & dosage, Genetic Vectors/genetics, Lentivirus/genetics, Lentivirus/physiology, Mice, Mice, Inbred DBA, Microscopy, Fluorescence, Peptide Elongation Factor 1/genetics, Phosphoglycerate Kinase/genetics, Promoter Regions, Genetic/genetics, Retina/metabolism, Retinal Degeneration/therapy, Rhodopsin/genetics, Virus Inactivation
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 13:59
Last modification date
20/08/2019 13:31
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