Adeno-associated virus (AAV) vectors have the potential to replace conventional anti-retroviral therapies, or even protect against an initial HIV-1 infection. The potential of AAV vectors arises from two properties: their exceptional safety profile, and their ability to sustain very high levels of transgene expression for years. A self-complementary AAV (scAAV) vector can sustain expression of 100-200 pg/ml of protein inhibitors for more than two years. In contrast, transgene expression from a conventional, single-stranded (ssAAV) vector is more than ten-fold lower. However, scAAV transgenes are necessarily half the size of ssAAV transgenes. This limit precludes expression of full-length antibodies, and instead requires use of non-native antibody-like molecules such as single-chain immunadhesins (scFv-Fc). Moreover, the size limitation of scAAV vectors prevents inclusion of other useful molecules, for example the joining (J) chains essential for IgA multimerization, and proteins and regulatory regions useful in various

Public Health Relevance

Adeno-associated virus (AAV) vectors have the potential to replace conventional anti-retroviral therapies, or even protect against an initial HIV-1 infection. This project will evaluate several variations of AAV vectors and transgenes to determine which are best at controlling HIV-1 replication, and which are best at preventing HIV-1 transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI100263-01
Application #
8311211
Study Section
Special Emphasis Panel (ZAI1-RB-A (J1))
Project Start
2012-04-01
Project End
2012-11-30
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
1
Fiscal Year
2012
Total Cost
$436,723
Indirect Cost
$110,554
Name
Harvard University
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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Gruntman, Alisha M; Bish, Lawrence T; Mueller, Christian et al. (2013) Gene transfer in skeletal and cardiac muscle using recombinant adeno-associated virus. Curr Protoc Microbiol Chapter 14:Unit 14D.3
Venkatesh, Aditya; Ma, Shan; Langellotto, Fernanda et al. (2013) Retinal gene delivery by rAAV and DNA electroporation. Curr Protoc Microbiol Chapter 14:Unit 14D.4
Ahmed, Seemin Seher; Li, Jia; Godwin, Jonathan et al. (2013) Gene transfer in the liver using recombinant adeno-associated virus. Curr Protoc Microbiol Chapter 14:Unit14D.6