This is a competitive renewal for Penn's P30 NIDDK Center on Molecular Therapy for Cystic Fibrosis and Genetic Diseases which has been in place since 1993. At the last renewal we shifted our strategy from a focus on clinical trials to vector discovery and distribution with an increased emphasis on immunology and animal models. This has had the desired result of substantially fueling a robust pipeline of promising preclinical programs that are entering clinical trials with better technology and an enhanced understanding of vector biology necessary for clinical success. With encouragement from NIDDK, we expanded access to our Cores to investigators outside of Penn to establish important strategic collaborations. During this cycle of the grant, Vector Core services increased from 576 in year 11 of the grant to 1458 projected for the current year (year 15). The substantial expansion of gene and cell therapy research associated with our Center is due in large part to the availability of new AAV and lentiviral technology discovered at Penn and distributed through our Vector Core. An important aspect of this expansion has been in the area of immunology that has emerged as a major impediment to success. The Center has aggressively recruited the participation of scientists interested in applied immunology and genetic vaccines to focus on issues relevant to gene and cell therapy. The current research base is substantial and strong across all areas relevant to the Center. Current total annual direct costs of grants awarded to Center Participants has been organized into the following three areas: Genetic Diseases, Stem Cells and Gene Transfer - $49 mil;Cystic Fibrosis - $8.6 mil;and Immunology and Vaccines -$14.9 mil. The Pjlot Grant program remains strong and has been useful in supporting young investigators and encouraging the participation of new investigators. Important recruitments at Penn have provided the opportunity to enhance leadership of the Center's Cores. This application requests support for Pilot Grants as well as the following Cores: Vector, Immunology, Cell Morphology and Animal Models.

Public Health Relevance

The Gene Therapy Program at Penn provides leadership and support to a diverse array of both Penn and external investigators in the area of cell and gene therapy for cystic fibrosis and genetic diseases. The program advises Center Participants with accumulated expertise as well as provided cutting-edge viral-vector technology and immune response analysis through the Vector and Immunology Cores - Such interactions have fueled the progression of two important gene therapies into clinical trials in the last funding period and will continue to do so in the future periods.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Center Core Grants (P30)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-1 (J2))
Program Officer
Mckeon, Catherine T
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Schools of Medicine
United States
Zip Code
Baek, Jeong-In; Choi, Soo Young; Chacon-Heszele, Maria F et al. (2014) Expression of Drosophila forkhead transcription factors during kidney development. Biochem Biophys Res Commun 446:15-7
Adam, Virginie S; Crosariol, Marco; Kumar, Sachin et al. (2014) Adeno-associated virus 9-mediated airway expression of antibody protects old and immunodeficient mice against influenza virus. Clin Vaccine Immunol 21:1528-33
Xiao, Yan; Nagai, Yasuhiro; Deng, Guoping et al. (2014) Dynamic interactions between TIP60 and p300 regulate FOXP3 function through a structural switch defined by a single lysine on TIP60. Cell Rep 7:1471-80
Chacon-Heszele, Maria F; Zuo, Xiaofeng; Hellman, Nathan E et al. (2014) Novel MAPK-dependent and -independent tubulogenes identified via microarray analysis of 3D-cultured Madin-Darby canine kidney cells. Am J Physiol Renal Physiol 306:F1047-58
Mays, Lauren E; Wang, Lili; Lin, Jianping et al. (2014) AAV8 induces tolerance in murine muscle as a result of poor APC transduction, T cell exhaustion, and minimal MHCI upregulation on target cells. Mol Ther 22:28-41
Nagai, Y; Limberis, M P; Zhang, H (2014) Modulation of Treg function improves adenovirus vector-mediated gene expression in the airway. Gene Ther 21:219-24
O'Neill, S M; Hinkle, C; Chen, S-J et al. (2014) Targeting adipose tissue via systemic gene therapy. Gene Ther 21:653-61
Huang, Liwei; Lipschutz, Joshua H (2014) Cilia and polycystic kidney disease, kith and kin. Birth Defects Res C Embryo Today 102:174-85
Myint, Melissa; Limberis, Maria P; Bell, Peter et al. (2014) In vivo evaluation of adeno-associated virus gene transfer in airways of mice with acute or chronic respiratory infection. Hum Gene Ther 25:966-76
Bryant, Laura M; Christopher, Devin M; Giles, April R et al. (2013) Lessons learned from the clinical development and market authorization of Glybera. Hum Gene Ther Clin Dev 24:55-64

Showing the most recent 10 out of 206 publications