- ASSISTANT PROFESSOR Developmental and Regenerative Biology
- ASSISTANT PROFESSOR Microbiology
- ASSOCIATE PROFESSOR Medicine, Cardiology
B.S., College Schaffhausen
M.Sc., Swiss Federal Institute of Technology
Dr. sc. nat. (Ph.D), Swiss Federal Institute of Technology
Postdoctorate, Memorial Sloan Kettering Cancer Center
Adeno-Associated Virus (AAV) Biology and AAV Gene Therapy
Gene therapy is a promising platform to treat and potentially cure currently intractable disorders. Among the most promising gene delivery vehicles are vectors based on adeno-associated virus (AAV).
AAV is particularly attractive because:
1) It is not known to be associated with any disease.
2) Recombinant AAV vectors can trigger long-term gene expression even in the absence of genome integration (at least in postmitotic tissues).
3) AVV vectors display only limited immunogenicity.
Due to these favorable properties, enthusiasm for gene therapy vectors based on adeno-associated virus (AAV) has steadily increased among researchers over the last few years. In fact, as of July 2015, 137 clinical trials using AAV have either been completed or are in progress. Moreover, the treatment of lipoprotein lipase deficiency with an AAV vector has been approved for clinical use in Europe, which is the first approval of gene therapeutic treatment in the Western World.
The research in our lab is focused on four areas:
1) The design of AAV variants with tissue and cell-specific tropism and increased resistance to pre-existing antibodies against the common AAV serotypes.
2) The development of AAV alternative approaches to overcome the hurdle that pre-existing anti-AAV antibodies pose to allow the use of AAV gene therapy for the broadest possible population segment.
3) To understand the basic biology of wild-type and recombinant AAV, especially as it relates to endocytosis and intracellular trafficking.
Nonnenmacher M, van Bakel H, Hajjar RJ, Weber T. High Capsid-Genome Correlation Facilitates Creation of AAV Libraries for Directed Evolution. Molecular Therapy 2015 Jan;.
Nonnenmacher ME, Cintrat JC, Gillet D, Weber T. Syntaxin 5-Dependent Retrograde Transport to the trans-Golgi Network Is Required for Adeno-Associated Virus Transduction. Journal of virology 2015 Feb; 89(3).
Nonnenmacher M, Weber T. Intracellular transport of recombinant adeno-associated virus vectors. Gene therapy 2012 Jun; 19(6).
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.
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.
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).
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.
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 2015 and/or 2016: 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. Patients may wish to ask their physician about the activities they perform for companies.
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