HMS Virology

Virology Faculty Member - Luk Vandenberghe Ph.D.

Luk Vandenberghe

Assistant Professor in Ophthalmology
Director, Grousbeck Gene Therapy Center
Director, Gene Transfer Vector Core
Associate Director, Ocular Genomics Institute

Schepens Eye Research Institute and Mass Eye and Ear
20 Staniford Street
Boston, MA 02114

Tel: 617-573-6993
Fax: 617-912-0114
Lab Members: 2 graduate students, 4 postdoctoral fellows, 1 staff scientist, 1 research assistant, 2 senior scientists

The Vandenberghe laboratory deconstructs viral evolution aiming to more profoundly understand capsid structure-function relationships and use this information to build improved viral vectors for gene therapy. For many of these studies, we use the ssDNA mammalian adeno-associated virus (AAV) as a model. AAV is not only one of the smallest and simplest mammalian viruses, it has also captivated the world of gene therapy as AAV, with remarkable efficiency and safety, is able to deliver and transduce genetic cargo into therapeutic target tissues such as the retina, liver, and CNS. AAVs come in many flavors that were originally distinguished based on serology, but now are more and more phylogenetically and structurally defined. Different AAVs demonstrate very distinct phenotypes (tropism, receptor use, host response, assembly, etc.) as a wild type virus or replication-defective vector. We are interested in functionally and structurally understanding the mechanism of these stark differences from the perspective of virus as well as host. One avenue towards this goal is to study the evolutionary biology of this virus, and use mathematical, statistical, and systems approaches in combination with empirical and molecular methods to shed light on the structure-function relationship of these small, yet intricately complex infectious protein assemblies. We aim at integrating these findings into improved technologies for therapeutic gene transfer, and use these findings and novel reagents toward building innovative therapies for diseases with unmet need, with a particular focus on blinding and hearing disorders.

Last Update: 5/14/2015


Bell, C.L., Vandenberghe, L.H., Bell, P., Limberis, M.P., Gao, G.P., Van Vliet, K., Agbandje-McKenna, M., and Wilson, J.M. (2011). The AAV9 receptor and its modification to improve in vivo lung gene transfer in mice. J Clin Invest 121, 2427-2435.

Vandenberghe, L.H., Bell, P., Maguire, A.M., Cearley, C.N., Xiao, R., Calcedo, R., Wang, L., Castle, M.J., Maguire, A.C., Grant, R., et al. (2011). Dosage thresholds for AAV2 and AAV8 photoreceptor gene therapy in monkey. Sci Transl Med 3, 88ra54.

Vandenberghe, L.H., Breous, E., Nam, H.J., Gao, G., Xiao, R., Sandhu, A., Johnston, J., Debyser, Z., Agbandje-McKenna, M., and Wilson, J.M. (2009). Naturally occurring singleton residues in AAV capsid impact vector performance and illustrate structural constraints. Gene Ther 16, 1416-1428.

Vandenberghe, L.H., Wang, L., Somanathan, S., Zhi, Y., Figueredo, J., Calcedo, R., Sanmiguel, J., Desai, R.A., Chen, C.S., Johnston, J., et al. (2006). Heparin binding directs activation of T cells against adeno-associated virus serotype 2 capsid. Nat Med 12, 967-971.

Vandenberghe, L.H., Wilson, J.M., and Gao, G. (2009). Tailoring the AAV vector capsid for gene therapy. Gene Ther 16, 311-319.

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