Genetic modification of the human genome to resist HIV-1 infection and/or disease progression
The proposed studies describe the genetic approaches utilizing human embryonic stem cells to suppress and/or eliminate the expression of the human protein CCR5. CCR5 is found on the surface of white blood cells. HIV-1 attaches to CCR5 and uses CCR5 to enter into its target cells. Our approach is to utilize established as well as new non-established approaches to prevent CCR5 from appearing on the surface of the cells. If CCR5 is not present, HIV-1 cannot infect the cells. Interestingly, this concept has already been proven in nature. Approximately 1% of the Caucasian population is genetically deficient for CCR5 and these individuals are resistant to HIV-1 transmission. Their white blood cells, when placed in culture, also resist HIV-1 infection in the laboratory. As such, we believe that our approach can be used to protect high risk individuals from HIV-1 infection as well as impede or stop progression of disease in those individuals already infected.
According to the Centers for Disease Control, California is second only to New York of individuals living with AIDS. Developing means to stop HIV-1 infection and cure those individuals already infected with HIV-1 is of paramount importance for the state of California.
The overall goal of this project is to investigate the use of embryonic stem cells and blood stem cells as a potential therapeutic approach for HIV-1 disease. We investigated a process known as RNA interference to block HIV-1 infection. We characterize the properties of cells carrying RNA interference to HIV-1 and developed new tools to facilitate the study.
- Nat Protoc (2012) Arrayed cellular microenvironments for identifying culture and differentiation conditions for stem, primary and rare cell populations. (PubMed: 22422316)
- J Gene Med (2010) Inhibition of HIV-1 infection by a unique short hairpin RNA to chemokine receptor 5 delivered into macrophages through hematopoietic progenitor cell transduction. (PubMed: 20186995)
- PLoS One (2010) Live cell monitoring of hiPSC generation and differentiation using differential expression of endogenous microRNAs. (PubMed: 20676373)
- Biomaterials (2010) Long-term human pluripotent stem cell self-renewal on synthetic polymer surfaces. (PubMed: 20817292)
- Genet Vaccines Ther (2009) Characterization of a potent non-cytotoxic shRNA directed to the HIV-1 co-receptor CCR5. (PubMed: 19515239)