Our goal in the first year of the grant has been to establish a mouse model for HIV infection using hematopoietic stem and progenitor cells (HSPC) from healthy adult donors and to create a series of novel RNA-based vectors that will provide resistance to HIV infection in the progeny of these cells. Dr. DiGiusto’s group has successfully demonstrated the ability to reliably engrafted mice with human immune system cells derived from adult HSPC. Among the engrafted cells are CD4+ T-cells and monocytes, the target cells for HIV infection. We have also demonstrated that we can expand the number of HSPC from each donor and maintain their ability to support engraftment of the mice with human T-cells and monocytes. This means that we are able to make a large number of mice with which to screen genetic therapies for HIV. During this period, Dr. Rossi’s group has created a 5 new anti-HIV viral vectors that can be used to genetically modify HSPC and impart HIV resistance to the T-cells and monocytes that are derived from these HSPC. Assays performed in culture dishes indicate that 3 of these vectors are very potent HIV inhibitors. Addionally, the vectors contain a gene that will allow us to selectively enrich for those HSPC that carry the gene under specific culture conditions. Thus, we can produce a population highly enriched for disease resistant HSPC. We are now beginning testing of anti-HIV vectors in our mouse model to establish which would be the best for moving towards clinical trials. The ultimate goal of the study is to define the best clinical candidate and we on track for meeting that goal within the timeframe of the grant.