In vivo adenovirus-mediated gene transfer into ocular tissues.
Replication-deficient adenoviruses have been successfully used to transfer foreign DNA into a variety of cells including post-mitotic cells, in vivo. In the eyes, most of the cells are quiescent or slowly dividing. They constitute the obligatory targets of gene transfer for a number of ocular diseases that have been elucidated at the molecular level and are potential targets for gene therapy. We have therefore analysed the ability of an adenovirus vector to transfer in vivo the Escherichia coli lacZ gene into ocular cells of mice. Injection of up to 3 x 10(7) p.f.u. into the vitreous body, the anterior chamber or the peribulbar space, did not result in any detectable cytopathic effect and was associated with endocytosis of viral particles in corneal endothelial, photoreceptor, bipolar, ganglionic and oculomotor muscle cells, depending on the administration route. At the viral titer used (3 x 10(7) p.f.u.), the expression was detected for at least 50 days. These results open new prospects for the treatment of some retinal hereditary disorders and acquired corneal or retinal alterations due to inflammatory disease.
Mashhour
B
B
CIF 90-03 Institut National de la Santé et de la Recherche Médicale, Institut Cochin de Génétique Moléculaire (ICGM), Paris, France.
Couton
D
D
Perricaudet
M
M
Briand
P
P
D000256:Adenoviridae / Q000235:genetics* / Q000472:pathogenicity; D000818:Animals; D003588:Cytopathogenic Effect, Viral; D004926:Escherichia coli / Q000235:genetics; D005123:Eye / Q000033:anatomy & histology / Q000378:metabolism*; D005128:Eye Diseases / Q000628:therapy; D015870:Gene Expression; D018014:Gene Transfer Techniques / Q000009:adverse effects; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007267:Injections; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D013997:Time Factors; D014822:Vitreous Body; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D001616:beta-Galactosidase