The overall goal of this core is to provide scientific and technical support for clinical and laboratory projects that require the use of recombinant retroviral vector technology and hematopoietic stem cell purification.
The specific aims are: 1. To provide technical and logistical support for the implementation of human gene therapy trials for HIV. This Core will serve as a reference source for clinicians engaged in research in the area of gene therapy for HIV infection. The Core will provide technical assistance for studies requiring BSL-3 and GLP guidelines in the following areas: I) large scale purification of hematopoietic progenitors; ii) large-scale transduction of hematopoietic progenitors; iii) assessment of vector presence in mature hematopoietic cells and in bone marrow progenitors, and iv) follow-up assays in patient samples for the development of replication competent retrovirus (RCR) according to FDA regulations. The Core will provide scientific advice in the following ares: I) FDA regulations governing the conduct of human gene therapy trials; ii) issues related to retroviral vectoring, including choice of envelope and producer cell line, manufacturing of viral supernatant under GMP conditions, titration assays,, use of cytokine combinations and other ancillary products during transduction, and iii) current guidelines and protocols available for toxicology testing in gene therapy, including assays to detect RCR and vector mediated immune responses. 2. To provide technical and logistical support to basic science research in gene therapy, hematopoiesis and pathogenesis of HIV infection. This Core will maintain stocks of HSC characterized by source, purity, gender and HLA haplotype for use in basic science projects in SCID-hu in vivo modeling experiments. The Core will also serve as a banking source for common retroviral packaging cell lines, reporter genes and packaging plasmids. The Core will also serve as a scientific and technical reference to basic science groups in the performance of laboratory assays commonly used in hematopoiesis and gene therapy research, including use of retroviral vectors, manufacturing of producer lines, isolation of highly primitive stem cell populations by functional assays and the performance of clonogenic assays. 3. To sere as an interface between clinical and basic science research groups by coordinating and regulating the use of clinical specimens in basic science research. Specimens from clinical trials will be banked and inventories in the Core, which will serve as a source of patient samples for basic sciences projects of hematopoiesis, gene therapy and HIV pathogenesis. Sample swill include CD34+ cells transduced with various anti-HIV reagents and follow-up blood and bone marrow samples from patients participating in gene therapy protocols.
Showing the most recent 10 out of 942 publications
