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 #
7P01AI100263-02
Application #
8574229
Study Section
Special Emphasis Panel (ZAI1-RB-A)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$756,630
Indirect Cost
$20,880
Name
Scripps Florida
Department
Type
DUNS #
148230662
City
Jupiter
State
FL
Country
United States
Zip Code
33458
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Wang, Dan; Gao, Guangping (2014) State-of-the-art human gene therapy: part II. Gene therapy strategies and clinical applications. Discov Med 18:151-61
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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