Abstract

The overall objective for this NCDDG application is to evaluate different methods for efficient delivery to toxin genes as a gene therapy approach for Acquired Immune Deficiency Syndrome (AIDS). Plasmid and retroviral constructs were previously generated from which toxin gene expression was controlled by HIV-1 regulatory proteins Tat and Rev. Stable cell lines were derived which had been transfected or infected with DT-A-encoding plasmids or retroviruses, respectively. Such cell lines were markedly impaired in their ability to be infected by laboratory to improve the efficiency of transfection of the toxin gene. (Project 9001) will serve as an animal core, to evaluate the in vivo anti-HIV effectiveness of toxin genes, delivered by methods described in Projects 1-2. The experiments described here should lead directly to preclinical safety and toxicity studies for HIV- regulated toxin genes. Ultimately, we hope HIV regulated toxin gene expression can be developed 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 #
1U01AI035231-01
Application #
2070747
Study Section
Special Emphasis Panel (SRC (47))
Project Start
1994-01-01
Project End
1996-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
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
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; 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
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

Showing the most recent 10 out of 14 publications