[Frontiers in Bioscience E4, 2546-2557, June 1, 2012]

Gene therapy in age related macular degeneration and hereditary macular disorders

Kati Kinnunen1,2,3, Seppo Yla-Herttuala3,4,5

1Department of Ophthalmology, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland, 2Department of Ophthalmology, Kuopio University Hospital, P.O. Box 1777, FIN-70211 Kuopio, Finland, 3Department of Biotechnology and Molecular Medicine, A.I.Virtanen Institute, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland, 4Department of Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland, 5Gene Therapy Unit, Kuopio University Hospital, P.O. Box 1777, FIN-70211Kuopio, Finland

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Viral vectors
3.1. AAV
3.2. Adenovirus
3.3. Lentivirus
3.4. Baculovirus
4. Non-viral vectors
5. Gene therapy in age related macular degeneration
5.1. PEDF
5.2. sFlt-2
5.3. RNA interference
6. Gene therapy in hereditary macular disorders
7. Summary and perspectives
8. Acknowledgments
9. References

1. ABSTRACT

In ophthalmology, administration of the therapeutic agent can be difficult due to the tight barriers in the eye. Multiple injections may be needed to allow the therapeutic agent to reach adequate levels in retina and choroidea which may increase the risk of complications including endophthalmitis, cataract and haemorrhages. Optimal methods for the delivery of therapeutic agents to the posterior segments of the eye have not yet been developed. Gene therapy offers an alternative where the therapeutic protein or proteins can be induced in the target tissue for a prolonged period of time after a single injection. The eye is a promising target for gene therapy due to its small size and tissue boundaries preventing leakage of the therapeutic material to other tissues or systemic circulation. However, most of the work in ocular gene therapy is still at the preclinical phase; only three vectors have reached phase 1/2 clinical trials. This review summarizes basic principles and current status of gene therapy in age related macular degeneration and hereditary macular disorders.