Diphtheria Toxin a Containing Retroviral and Adeno Associated Virus Vectors

Harrison, Gail S.

Abstract

The goal for Project 1 is to develop stocks of recombinant retroviral and adeno-associated viral vectors containing an HIV-regulated diphtheria toxin A chain gene. Based on our previous studies, such vectors should confer resistance to HIV infection, due to activation of the toxin gene early in HIV infection, before production of viral progeny. We will optimize conditions for efficient transduction into human peripheral blood mononuclear cells and bone marrow cells in culture, and rigorously assay for HIV production in transduced cells. I collaboration with Project 9001 we will also examine the in vivo anti- HIV properties of these vectors in the SCID/AIDS mouse model. Project 1 will additionally supply all HIV-regulated toxin constructs to Projects 2 for their studies. The experiments described here should lead directly to preclinical safety and toxicity studies for HIV-regulated toxin gene expression as a therapy for AIDS, where the immune system would be reconstituted with self-renewing, immune-competent cells which are resistant to HIV infection.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Research Project--Cooperative Agreements (U01)
• Project #: 5U01AI035231-02
• Application #: 3727637
• Support Year: 2
• Fiscal Year: 1995

Institution

• Name: University of Colorado Denver
• DUNS #: 065391526
• City: Aurora
• State: CO
• Country: United States
• Zip Code: 80045

Publications

Slepushkin, Vladimir; Simoes, Sergio; de Lima, Maria C Pedroso et al. (2004) Sterically stabilized ph-sensitive liposomes. Methods Enzymol 387:134-47

Simoes, S; Slepushkin, V; Gaspar, R et al. (1999) Successful transfection of lymphocytes by ternary lipoplexes. Biosci Rep 19:601-9

Simoes, S; Slepushkin, V; Pretzer, E et al. (1999) Transfection of human macrophages by lipoplexes via the combined use of transferrin and pH-sensitive peptides. J Leukoc Biol 65:270-9

Duzgunes, N; Pretzer, E; Simoes, S et al. (1999) Liposome-mediated delivery of antiviral agents to human immunodeficiency virus-infected cells. Mol Membr Biol 16:111-8

de Lima, M C; Simoes, S; Pires, P et al. (1999) Gene delivery mediated by cationic liposomes: from biophysical aspects to enhancement of transfection. Mol Membr Biol 16:103-9

Konopka, K; Duzgunes, N; Rossi, J et al. (1998) Receptor ligand-facilitated cationic liposome delivery of anti-HIV-1 Rev-binding aptamer and ribozyme DNAs. J Drug Target 5:247-59

Simoes, S; Slepushkin, V; Gaspar, R et al. (1998) Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides. Gene Ther 5:955-64

Konopka, K; Rossi, J J; Swiderski, P et al. (1998) Delivery of an anti-HIV-1 ribozyme into HIV-infected cells via cationic liposomes. Biochim Biophys Acta 1372:55-68

Van Parijs, L; Abbas, A K (1998) Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science 280:243-8

Konopka, K; Harrison, G S; Felgner, P L et al. (1997) Cationic liposome-mediated expression of HIV-regulated luciferase and diphtheria toxin a genes in HeLa cells infected with or expressing HIV. Biochim Biophys Acta 1356:185-97