In vivo gene transfer into the retina mediated by a novel liposome system.
OBJECTIVE
To determine whether a reporter gene can be introduced into rat and mouse retinas in vivo using the authors' novel liposome system.


METHODS
Cytomegalovirus-promoted LacZ genes and nonhistone nuclear protein, high mobility group 1 (HMG1), were coencapsulated in liposomes by agitation and sonication. The liposomes were then coated with the envelope of inactivated hemagglutinating virus of Japan (HVJ; Sendai virus) by fusion (HVJ liposome). The HVJ liposome solution was injected into the vitreous cavity of adult Sprague-Dawley rats (n = 30) or the subretinal space of adult CD-1 mice (n = 42). LacZ expression was assessed by beta-galactosidase assay.


RESULTS
LacZ expression was demonstrated in the photoreceptors as long as 30 days after intravitreal and subretinal injections. beta-Gal activity was observed also in neurons and glial cells in the ganglion cell layer of the intravitreally injected rats and, although at lower intensity, in the retinal pigment epithelium of both animals. No inflammation or toxic effects secondary to the HVJ liposomes were detected on histologic examination.


CONCLUSIONS
In vivo transfer and expression of a reporter gene into adult mammalian retina can be achieved using HVJ liposomes. This method offers a promise as a nonviral system for in vivo gene transfer into adult mammalian neural retina.
Hangai
M
M
Department of Ophthalmology and Visual Science, Graduate School of Medicine, Kyoto University, Japan.
Kaneda
Y
Y
Tanihara
H
H
Honda
Y
Y
D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006609:High Mobility Group Proteins / Q000235:genetics; D007124:Immunoenzyme Techniques; D007267:Injections; D007763:Lac Operon / Q000235:genetics*; D008081:Liposomes; D008297:Male; D051379:Mice; D010222:Parainfluenza Virus 1, Human / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000201:enzymology* / Q000821:virology; D014822:Vitreous Body; D001616:beta-Galactosidase / Q000378:metabolism*
D006609:High Mobility Group Proteins; D008081:Liposomes; D001616:beta-Galactosidase