title: Stem cells as vehicles for gene therapy: novel strategy for HIV infection.
abstract: Restoration of bone marrow and immune function by means of allogeneic bone marrow transplantation has been attempted in AIDS patients but has not been successful as the donor-derived cells, or their progeny, inevitably became infected. A hairpin ribozyme that specifically cleaves HIV-1 RNA has been developed by F. Wong-Staal et al. and has been demonstrated to confer resistance against HIV-1 infection. Allogeneic transplantation of CD34+ cells or their pluripotent subsets, transduced by vectors bearing this ribozyme gene, can protect the stem cells and their progeny from HIV-1 infection and eventually restores immune function. We have provided evidence that long-term repopulating stem cells can be mobilized into peripheral blood by growth factors. The combination of G-CSF and GM-CSF seems to yield a high frequency of pluripotent stem cells with a CD34+ subset profile that is similar to placental and umbilical cord blood (PUCB). We have then demonstrated a highly efficient transduction of CD34+ cells from PUCB and mobilized leukapheresis products by retroviral vectors bearing the ribozyme gene. Expression of the ribozyme gene, as shown by reverse transcriptase-polymerase chain reaction, was of similar magnitude (70%-90% of cells that grow into colonies). Challenge of the progeny macrophages from such transduced CD34+ cells with monocyte-trophic strains of HIV-1 showed that they were resistant to infection. Thus allogeneic transplantation of CD34+ cells or their pluripotent subsets, transduced with ribozyme gene, can be a promising strategy for the treatment of HIV infection.
authors: Department of Medicine, University of California, San Diego, USA.
authors: A D
authors: AD
authors: Ho
authors: X
authors: X
authors: Li
authors: T A
authors: TA
authors: Lane
authors: M
authors: M
authors: Yu
authors: P
authors: P
authors: Law
authors: F
authors: F
authors: Wong-Staal
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000628:therapy*; D000328:Adult; D018952:Antigens, CD34 / Q000276:immunology; D015316:Genetic Therapy; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D016131:Lymphocyte Subsets; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D018952:Antigens, CD34; D016337:RNA, Catalytic