SBIR-STTR Award

Using a method of retroviral gene transduction we have been able to generate conditionally immortalized long-term hematopoietic stem cell lines from primary mouse bone marrow stem cells. Phase I of this project includes testing the same technology in human cells and the subsequent analysis of those cells in the laboratory and in mice. In addition, the project includes knockdown of HIV-1 co-receptors to generate HIV-1 resistant cells in a mouse model. The method to genetically modify the long-term hematopoietic stem cell lines includes state-of-the-art vector transduction with shRNA containing constructs. Phase II of the project will entail testing this approach in a primate model and optimizing large-scale production of genetically-modified conditionally-immortalized long-term hematopoietic stem cells for testing in clinical trials. This project seeks to refine appropriate methods to genetically manipulate conditionally immortalized hematopoietic stem cell lines to generate HIV-1 resistant cells. Once these methods have been established for the human, the long-term goal to benefit public health will be to use these cells for treating HIV-1 infected patients to re-establish a functional immune system that is protected from endogenous or exogenous sources of HIV.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
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Using a method of retroviral gene transduction we have been able to generate conditionally immortalized long-term hematopoietic stem cell lines from primary mouse blood stem cells. Phase I of this project included applying this technology to generate human cell lines. In addition, the project included testing a non-viral method to generate the stem cell lines from mice. Phase II of the project will entail optimizing large-scale production of protein transduced long-term hematopoietic stem cells from human cells that are resistant to HIV infection for eventual testing in larger animals and human clinical trials.

Public Health Relevance:
This project seeks to optimize a novel method to generate large amounts of human blood stem cells for clinical use in the prevention and treatment of HIV infection. Once this method has been validated for large-scale production, the long-term goal for benefiting public health will be to use this system to generate HIV resistant cells in infected individuals or in populations that are at-risk for acquiring the HIV virus.

Thesaurus Terms:
"0-11 Years Old; 21+ Years Old; Aids Virus; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Adult; Animal Model; Animal Models And Related Studies; Animals; Blood; Blood Cells; Blood Precursor Cell; Bone Marrow Stem Cell; Bone Marrow Stem Cell Transplantation; Bone Marrow Transplant; Bone Marrow Transplantation; C-C Ckr-5 Gene; C-C Chemokine Receptor Type 5 Gene; Cc-Ckr-5 Gene; Ccckr5 Gene; Ccr-5 Gene; Ccr5; Ccr5 Gene; Cd195 Antigen Gene; Chemr13 Gene; Ckr-5 Gene; Ckr5 Gene; Cmkbr5 Gene; Cancers; Cell Line; Cell Lineage; Cell Lines, Strains; Cell Surface; Cellline; Cells; Chemokine (C-C) Receptor 5 Gene; Child; Child Youth; Children (0-21); Chimera Protein; Chimeric Proteins; Clinical; Clinical Trials; Clinical Trials, Unspecified; Development; Engraftment; Fusion Protein; Generations; Genetic; Goals; Grafting, Bone Marrow; Hiv; Hiv Infections; Hiv-1 Fusion Co-Receptor Gene; Htlv-Iii; Htlv-Iii Infections; Htlv-Iii-Lav Infections; Hematopoietic Cell Tumor; Hematopoietic Malignancies; Hematopoietic Neoplasms; Hematopoietic Neoplasms Including Lymphomas; Hematopoietic Tumor; Hematopoietic And Lymphoid Cell Neoplasm; Hematopoietic And Lymphoid Neoplasms; Hematopoietic Stem Cells; Hematopoietic, Including Myeloma; Heterograft; Human; Human Cell Line; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type Iii; Human T-Cell Lymphotropic Virus Type Iii; Human T-Lymphotropic Virus Type Iii; Human, Adult; Human, Child; Human, General; Immune; Immunodeficiency Disorder; Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Immunological Deficiency Syndromes; In Vitro; Individual; Investigators; Lav-Htlv-Iii; Lentivirinae; Lentivirus; Lymphadenopathy-Associated Virus; Malignant Hematopoietic Neoplasm; Malignant Neoplasms; Malignant Tumor; Mammals, Mice; Man (Taxonomy); Man, Modern; Marrow; Marrow Transplantation; Methods; Mice; Modification; Mother Cells; Murine; Mus; Patients; Peripheral Blood Cell; Phase; Phenotype; Populations At Risk; Prevention; Production; Progenitor Cell Transplantation; Progenitor Cells; Progenitor Cells, Hematopoietic; Programs (Pt); Programs [publication Type]; Proteins; Public Health; Radiation; Receptor Protein; Recombinants; Research; Research Personnel; Researchers; Resistance; Reticuloendothelial System, Blood; Sbir; Sbirs (R43/44); Safety; Small Business Innovation Research; Small Business Innovation Research Grant; Source; Stem Cell Transplantation; Stem Cell Transplant; Stem Cells; Subfamily Lentivirinae; System; System, Loinc Axis 4; T-Cells; T-Lymphocyte; T-Lymphotropic Virus Type Iii Infections, Human; Technology; Testing; Therapeutic; Thymus-Dependent Lymphocytes; Transduction Gene; Translating; Translatings; Transplantation; Transplantation, Heterologous; Vector Mediated Transfer Genes; Viral; Virus-Hiv; Virus-Lenti; Work; Xenograft; Xenograft Procedure; Xenotransplantation; Abstracting; Adult Human (21+); Base; Blood Cancer; Cell Type; Children; Clinical Applicability; Clinical Application; Clinical Investigation; Cultured Cell Line; Gene Product; Hypoimmunity; Immune Deficiency Disorder; Immunodeficiency; In Vivo; Language Translation; Large Scale Production; Macrophage; Malignancy; Model Organism; Neoplasm/Cancer; New Approaches; New Technology; Novel; Novel Approaches; Novel Strategies; Novel Strategy; Phase 2 Study; Pluripotency; Pre-Clinical; Preclinical; Programs; Public Health Medicine (Field); Public Health Relevance; Rapid Growth; Ray (Radiation); Receptor; Reconstitute; Reconstitution; Resistant; Safety Testing; Thymus Derived Lymphocyte; Tool; Transplant; Youngster"