Despite a wealth of pre-clinical animal studies over the past decade which had demonstrated the safety of gene therapy, the recent clinical experience of Cavazzana-Calvo, Fischer and co-workers with the treatment of children with SCID-X1 by gene therapy suggests that retroviral and lentiviral vector mediated gene therapies that employ existing technology may present a significant risk to patients. While there may be some difference in opinion with regard to the appropriateness of continuing clinical gene therapy studies that make use of existing technology, most would agree that the development of vectors with an improved safety profile would significantly accelerate the advancement of the clinical development of retroviral and lentiviral vector-based gene therapies. The proposed research program will focus on three technological areas of lentiviral vector development which we believe could have the most impact on safety profile of the vectors. These areas include the development of better and safer methods to produce lentiviral vectors suitable for clinical use, the development of more effective means to conditionally eliminate transduced cells and the development of methods to minimize the effects of lentiviral-mediated gene transfer on cellular gene expression. Overall, these studies should lead to the generation of valuable information, technology, and reagents that should be of broad interest to investigators working in the field of gene therapy, and should greatly accelerate the re-establishment of a strong clinical development effort in lentiviral vector-based gene therapy strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM079187-03
Application #
7634476
Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Okita, Richard T
Project Start
2007-08-01
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
3
Fiscal Year
2009
Total Cost
$321,971
Indirect Cost
Name
Harvard University
Department
Genetics
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Yen, Laising; Stockwell, Brent R; Mulligan, Richard C (2009) A mammalian cell-based assay for screening inhibitors of RNA cleavage. Methods Mol Biol 540:335-47