Organ-specific expression of the lacZ gene controlled by the opsin promoter after intravenous gene administration in adult mice.
BACKGROUND
The tissue-specific expression of an exogenous gene, under the influence of a tissue-specific promoter, has been examined in the past with pro-nuclear injections of the transgene and the development of transgenic mouse models. 'Adult transgenics' is possible with the acute expression of an exogenous gene that is administered to adult animals, providing the transgene can be effectively delivered to distant sites following an intravenous administration.


METHODS
The organ specificity of exogenous gene expression in adult mice was examined with a bacterial beta-galactosidase (LacZ) expression plasmid under the influence of the bovine rhodopsin gene promoter. The 8-kb plasmid DNA was delivered to organs following an intravenous administration with the pegylated immunoliposome (PIL) non-viral gene transfer technology. The PIL carrying the gene was targeted to organs with the rat 8D3 monoclonal antibody (MAb) to the mouse transferrin receptor (TfR).


RESULTS
The rhodopsin/beta-galactosidase gene was expressed widely in both the eye and the brain of adult mice, but was not expressed in peripheral tissues, including liver, spleen, lung, or heart. Ocular expression included the retinal-pigmented epithelium, the iris, and ciliary body, and brain expression was observed in neuronal structures throughout the cerebrum and cerebellum.


CONCLUSIONS
The expression of trans-genes in adult animals is possible with the PIL non-viral gene transfer method. The opsin promoter enables tissue-specific gene expression in the eye, as well as the brain of adult mice, whereas gene expression in peripheral tissues, such as liver or spleen, is not observed.
Department of Medicine, UCLA, Los Angeles, CA 90024, USA.
Chunni
C
Zhu
Yun
Y
Zhang
Yu-Feng
YF
Zhang
Jian
J
Yi Li
Ruben J
RJ
Boado
William M
WM
Pardridge
D000818:Animals; D001921:Brain / Q000378:metabolism; D005123:Eye / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007763:Lac Operon; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D010957:Plasmids; D011401:Promoter Regions, Genetic; D051381:Rats; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000235:genetics*; D019076:Transgenes; D001616:beta-Galactosidase / Q000235:genetics* / Q000378:metabolism
D008081:Liposomes; D011990:Receptors, Transferrin; D012243:Rhodopsin; D001616:beta-Galactosidase