INTRACELLULAR IMMUNIZATION VIA TAR DECOYS IN PBL

Project: Research project

Project Details

Description

The long-term objective of the proposed studies is to develop
intracellular immunization approaches for the treatment of AIDS. In the
course of the previous funding period, we have developed a novel
inhibition strategy utilizing TAR decoys to render CEM cells (a CD4+
human T-cell line) highly resistant to HIV replication. Towards the
development of a peripheral T-cell targeted approach for the treatment of
AIDS, I propose in this application to develop the conditions to transfer
HIV resistance to short-term cultures of peripheral CD4+ T cells (PBL)
obtained from human volunteers. In preliminary studies we have shown
that retroviral-mediated transfer of TAR decoy templates into normal CD4+
T cells led to a reduction of HIV replication and also provided a measure
of protection from the cytopathic effects of HIV. However, the extent of
inhibition observed in PBL was less dramatic than that observed in
previous studies using an established cell line (CEM).

The specific aims of the proposed studies are: (1) to improve the
effectiveness of the TAR decoy-mediated inhibition strategy, primarily by
increasing the concentration of TAR decoy RNA expressed in the cell.
This will be achieved by developing improved pol III-based systems
derived from tRNA and U6 snRNA genes. (2) To develop the conditions for
inhibition of HIV replication in cultured peripheral blood lymphocytes
obtained from HIV seronegative volunteers. Conditions will be sought
that maximize efficiency of retroviral transfer of TAR decoy templates
while minimizing ex-vivo manipulation of normal peripheral blood
lymphocytes.
StatusFinished
Effective start/end date7/1/926/30/02

Funding

  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases: $306,965.00
  • National Institute of Allergy and Infectious Diseases: $316,174.00

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