- ASSISTANT PROFESSOR Medicine, Cardiology
- ASSISTANT PROFESSOR Developmental and Regenerative Biology
- ASSISTANT PROFESSOR Microbiology
B.S., College Schaffhausen
Masters, Swiss Federal Institute of Technology
Dr. sc. nat. (Ph.D), Swiss Federal Institute of Technology
Chemistry and Biochemistry
Postdoctorate, Memorial Sloan Kettering Cancer Center
Adeno-Associated Virus (AAV) Biology and AAV Gene TherapyDue to its relative safety, enthusiasm for gene therapy vectors based on adeno-associated virus (AAV) has steadily increased among researchers over the last few years. As a result, AAV vectors are being used for a widening variety of therapeutic applications. AAV is particularly attractive because the wild-type virus can integrate its genome into a specific location on chromosome 19. Although recombinant AAV vectors, at present, do not have this property, active research aimed at developing such vectors is ongoing. Such vectors would have the advantage that they would not result in oncogenic transformation caused by random integration of vector DNA. Our lab is focusing on the cellular mechanisms that underlie the cell and tissue specificity of AAV. AAV can transduce a variety of cell types and tissues but with varying efficiencies depending on cell type. Muscle, for instance, is transduced very efficiently, while other tissues and cell types are transduced more poorly. These differences can only be partially explained by variations in receptor densities in various tissues and cell types. It is likely that other cellular barriers also are playing a role in these differences. Our research aims to gain a better understanding of the cellular roadblocks that prevent the efficient transduction of certain cell types and develop methods to improve transduction efficiencies for these cell types and tissues. Specifically, we are developing new methods to target AAV to specific cell types.
Postdoctoral Fellows: Mathieu Nonnenmacher
Rapti K, Louis-Jeune V, Kohlbrenner E, Ishikawa K, Ladage D, Zolotukhin S, Hajjar RJ, Weber T. Neutralizing Antibodies Against AAV Serotypes 1, 2, 6, and 9 in Sera of Commonly Used Animal Models. Molecular Therapy 2012; 20: 73-83.
Kohlbrenner E, Henckaerts E, Rapti K, Gordon RE, Linden RM, Hajjar RJ, Weber T. Quantification of AAV particle titers by infrared fluorescence scanning of coomassie-stained sodium dodecyl sulfate-polyacrylamide gels. Human gene therapy methods 2012 Jun; 23(3).
Nonnenmacher M, Weber T. Adeno-Associated Virus 2 Infection Requires Endocytosis through the CLIC/GEEC Pathway. Cell Host and Microbe 2011; 10: 563-576.
Zeltner N, Kohlbrenner E, Clément N, Weber T, Linden RM. Near-perfect infectivity of wild-type AAV as benchmark for infectivity of recombinant AAV vectors. Gene Therapy 2010; 17(7).
Hirosue S, Senn K, Clement N, Nonenmacher M, Gigout L, Linden RM, Weber T. Effect of inhibition of dynein function and microtubule-altering drugs on AAV2 transduction. Virology 2007; 367: 10-18.
Gigout L, Rebollo P, Clement N, Warrington KH, Muzyczka N, Linden RM, Weber T. Altering AAV tropism with mosaic viral capsids. Mol Ther 2005 Jun; 11(6): 856-865.
Hirosue S, Weber T. pH-Dependent Lytic Peptides Discovered by Phage Display. Biochemistry 2006 May 23; 45(20): 6476-87.
Weber T, Zemelman BV, Mcnew JA, Westermann B, Gmachl M, Parlati F, Sollner TH, Rothman JE. SNAREpins: minimal machinery for membrane fusion. Cell 1998 Mar 20; 92(6): 759-72.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Weber did not report having any of the following types of financial relationships with industry during 2013 and/or 2014: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
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