BBS Faculty Member - Luk Vandenberghe

Luk Vandenberghe

Department of Ophthalmology

Massachusetts Eye and Ear Infirmary
Schepens Eye Research Institute
20 Staniford St
Boston, MA 02114
Tel: 617-573-6993
Fax: 617-912-0114
Email: luk_vandenberghe@meei.harvard.edu
Visit my lab page here.

Research in the Vandenberghe Lab is focused on developing and translating genetic therapies to the clinic with an emphasis on blindness and other neurosensory disorders. We aim at defining and characterize hurdles for gene therapies in its path toward clinical reality. Our research aims to work to overcome these barriers by a) the study of the biology of human gene transfer, b) the development of enabling gene transfer technologies, and c) the translation of specific therapeutic programs.

Clinical trial success in a few gene therapy trials for inherited disorders, including one form of early onset retinal degeneration, has led to validation of the adeno-associated viral vector (AAV) platform. While AAV has several desirable properties and has proven safe and efficacious in these studies, several limitations of the vector system prevent its broad clinical application. It is exactly these limitations that are the focus of our studies which require a convergence of virology, structural and molecular biology, engineering, clinical medicine and immunology. Specifically, we are interested in improving gene delivery of large genes, in working toward therapeutic gene editing approaches, to expand the cellular targets and safety of current vectors, and to develop simple molecular circuitry that allows exogenous induction and regulation of transgene expression for human gene therapy. A second effort by members of the Vandenberghe lab is to build translational gene therapy programs for vision disorders targeting both inherited and complex disorders and both anterior and posterior segment. Currently, our laboratory is moving forward optogenetic therapies for retinal blinding disorders, as well as several programs in gene augmentation for single gene defects.

Last Update: 1/22/2014

Publications

For a complete listing of publications click here.

Vandenberghe LH, Xiao R, Lock M, Lin J, Korn M, Wilson JM. Efficient serotype-dependent release of functional vector into the culture medium during adeno-associated virus manufacturing. Human gene therapy 2010; 21(10): 1251-7.

Bell CL, Vandenberghe LH, Bell P, Limberis MP, Gao GP, Van Vliet K, Agbandje-McKenna M, Wilson JM. The AAV9 receptor and its modification to improve in vivo lung gene transfer in mice. The Journal of clinical investigation 2011; 121(6): 2427-35.

Vandenberghe LH, Bell P, Maguire AM, Cearley CN, Xiao R, Calcedo R, Wang L, Castle MJ, Maguire AC, Grant R, Wolfe JH, Wilson JM, Bennett J. Dosage thresholds for AAV2 and AAV8 photoreceptor gene therapy in monkey. Science translational medicine 2011; 3(88): 88ra54.

Vandenberghe, L.H.*,+, Bell, P*, Maguire, A.M., Xiao, R, Hopkins, T.B., Grant, G., Bennett, J. and Wilson, J.M.+. AAV9 targets cone photoreceptors in the nonhuman primate retina. Plos One. (accepted for publication)