Repeat administration of proteins to the eye with a single intraocular injection of an adenovirus vector.
Delivery of therapeutic proteins, such as antiangiogenic proteins, to the eye is a demonstrated method for the control of age-related macular degeneration (AMD). However, one of the key limitations is the requirement for frequent and repeated intraocular injections. In this article, we demonstrate that repeated protein production in the eye can be stimulated from the cytomegalovirus (CMV) promoter without repeat intraocular injections using a small molecule, all-trans retinoic acid (ATRA). ATRA by systemic delivery can stimulate protein production multiple times in the eye. Administration of ATRA resulted in stimulation of gene expression to relevant levels that block abnormal blood vessel growth in an experimental animal model for AMD. These data support the principles of this technological discovery to therapeutic applications for chronic ocular diseases.
McVey
Duncan
D
Vector Sciences, GenVec, Inc., Gaithersburg, Maryland, USA.
Hamilton
Melissa M
MM
Hsu
Chi
C
King
C Richter
CR
Brough
Douglas E
DE
Wei
Lisa L
LL
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D020256:Choroidal Neovascularization / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D003587:Cytomegalovirus / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D008156:Luciferases; D009414:Nerve Growth Factors; D015843:Serpins; D014212:Tretinoin; D000099174:Pigment Epithelium-Derived Factor