Building 6, Room 331B
6 Center Drive
Bethesda, Maryland 20892-0610
Phone: (301) 594-5376
Fax: (301) 480-9917
The ocular gene therapy laboratory was established to develop gene-based therapeutics for ocular diseases and to evaluate these novel drugs clinically. The laboratory also conducts research projects employing gene transfer technology to elucidate novel and exploitable mechanisms of pathology that cause ocular diseases. The purpose of this research is to identify new drug targets for the development of human therapeutics.
Prior to coming to the NEI, I directed research and development groups for 11 years at Avigen Inc., a small gene therapy company. During that time, groups under my direction developed several adeno-associated virus (AAV) vector-based gene therapeutics and invented a method to produce clinical-grade AAV gene therapy vectors. This work culminated in three Phase 1/2 clinical trials evaluating AAV vectors for the treatment of hemophilia B (clotting Factor IX deficiency) and Parkinson’s disease. I came to the NEI because I believe that ocular applications are among the most promising for AAV gene therapeutics and have the highest probability of clinical success. The laboratory has three major areas of interest: clinical development of AAV vector-based gene therapeutics, vector refinement including the reduction of preexisting immunity and small-molecule regulation of transgene expression, and basic research into the mechanisms of pathology of age-related macular degeneration and retinitis pigmentosa.
Our current areas of focus are:
- Clinical development of an AAV vector for the treatment of X-linked retinoschisis
- Development of AAV capsids for human intravitreal delivery that feature improved tropisms and human preexisting immunity profiles
- Development of a small molecule-regulated switch that can be used clinically
- Investigation of the early events in age-related macular degeneration
- Evaluation of novel growth factors and antiangiogenic molecules
- Park TK, Wu Z, Kjellstrom S, Zeng Y, Bush RA, Sieving PA, Colosi P. 2009.Intravitreal delivery of AAV8 retinoschisin results in cell type-specific gene expression and retinal rescue in the Rs1-KO mouse. Gene Ther. 16(7):916-26.
- Adeno-associated virus (AAV) capsid genes isolated from rat and mouse liver genomic DNA define two new AAV species distantly related to AAV-5. 2006. Lochrie MA, Tatsuno GP, Arbetman AE, Jones K, Pater C, Smith PH, McDonnell JW, Zhou SZ, Kachi S, Kachi M, Campochiaro PA, Pierce GF, Colosi P. Virology. 353(1):68-82.
- Mutations on the external surfaces of adeno-associated virus type 2 capsids that affect transduction and neutralization. 2006. Lochrie MA, Tatsuno GP, Christie B, McDonnell JW, Zhou S, Surosky R, Pierce GF, Colosi P. J Virol. 80(2):821-34.
- Novel caprine adeno-associated virus (AAV) capsid (AAV-Go.1) is closely related to the primate AAV-5 and has unique tropism and neutralization properties. 2005. Arbetman AE, Lochrie M, Zhou S, Wellman J, Scallan C, Doroudchi MM, Randlev B, Patarroyo-White S, Liu T, Smith P, Lehmkuhl H, Hobbs LA, Pierce GF, Colosi P. J Virol. 79(24):15238-45.
- Preclinical in vivo evaluation of pseudotyped adeno-associated virus vectors for liver gene therapy. 2003. Grimm D, Zhou S, Nakai H, Thomas CE, Storm TA, Fuess S, Matsushita T, Allen J, Surosky R, Lochrie M, Meuse L, McClelland A, Colosi P, Kay MA. Blood. 102(7):2412-9.