Pharmacologically regulated gene expression in the retina following transduction with viral vectors.
The availability of inducible expression systems makes regulatable control of therapeutic proteins an attainable goal in gene therapy. We delivered tetracycline-inducible transgenes to the subretinal space using recombinant adenoviruses. Upon administration of doxycycline, we demonstrated reversible expression of green fluorescent protein in the retinal pigment epithelium as well as modulation of human growth hormone produced in the retina and secreted in the blood stream. This mode of delivery and regulation offers a unique way to evaluate gene function in the eye and represents a novel method for introducing therapeutic proteins into the retina.
Dejneka
N S
NS
Department of Ophthalmology, Scheie Eye Institute, Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA 19104-6069, USA.
Auricchio
A
A
Maguire
A M
AM
Ye
X
X
Gao
G P
GP
Wilson
J M
JM
Bennett
J
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins; D019382:Human Growth Hormone / Q000235:genetics; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology; D014161:Transduction, Genetic / Q000379:methods*
D000900:Anti-Bacterial Agents; D008164:Luminescent Proteins; D019382:Human Growth Hormone; D049452:Green Fluorescent Proteins; D013752:Tetracycline; D004318:Doxycycline