原创力文档retinal degeneration progression changes lentiviral vector cell targeting in the retina视网膜变性过程变化慢病毒载体细胞定位在视网膜上.pdfVIP
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retinal degeneration progression changes lentiviral vector cell targeting in the retina视网膜变性过程变化慢病毒载体细胞定位在视网膜上
Retinal Degeneration Progression Changes Lentiviral
Vector Cell Targeting in the Retina
1 ´ 1 ´ 1 1 1
Maritza Calame , Maite Cachafeiro , Stephanie Philippe , Karine Schouwey , Meriem Tekaya , Dana
1 2,3 1 1
Wanner , Chamsy Sarkis , Corinne Kostic , Yvan Arsenijevic *
1 Unit of Gene Therapy and Stem Cell Biology, Service of Ophthalmology, Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland, 2 NewVectys SAS, Paris,
France, 3 Team of Biotherapy and Biotechnology, CRICM, UPMC-Paris6 UMR_S 975, INSERM U975, CNRS UMR 7225, Paris, France
Abstract
In normal mice, the lentiviral vector (LV) is very efficient to target the RPE cells, but transduces retinal neurons well only
during development. In the present study, the tropism of LV has been investigated in the degenerating retina of mice,
knowing that the retina structure changes during degeneration. We postulated that the viral transduction would be
increased by the alteration of the outer limiting membrane (OLM). Two different LV pseudotypes were tested using the
VSVG and the Mokola envelopes, as well as two animal models of retinal degeneration: light-damaged Balb-C and
Rhodopsin knockout (Rho-/-) mice. After light damage, the OLM is altered and no significant increase of the number of
transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the Rho-/- mice, an alteration of the OLM
was also observed, but the possibility of transducing photoreceptors was decreased, probably by ongoing gliosis. The use
of a ubiquitous promoter allows better photoreceptor
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