ANTISENSE RNA INHIBITION OF HIV VIA RETROVIRAL VECTORS

Project: Research project

Description

The objective of the proposed studies is to investigate the use of
antisense RNA inhibition as a method to render cells resistant to
infection and replication of human immunodeficiency virus (HIV).
The experimental strategy involves stable gene transfer of DNA
constructs, which serve as templates for the constitutive
expression of antisense RNA in the transduced cells. This
approach, also termed "intracellular immunization", contrasts with
the use antisense oligonucleotides. The proposed studies will focus on the design of HIV specific
antisense DNA templates which will be introduced into cultured
human lymphoid cell lines via retroviral vectors, and tested for
their ability to inhibit the replication of HIV. The major
objective of the proposed studies is to design vector systems
leading to efficient expression of antisense RNA in the target
cells by exploring (a) the use of three types of promoters for
antisense RNA expression: mammalian RNA polymerase II, human t-RNA
(pol III), and a bacteriophage T7 promoter, (b) the use of two
retroviral vector systems: the previously characterized N2 vector,
and double copy DC vectors, a novel type of vector which was
designed to improve the expression of transduced genes. Antisense
RNA inhibition mediated via stable gene transfer will be used to
study the mechanism of molecular and genetic regulation of HIV.
A long term objective of these studies is to develop a treatment
for AIDS in which bone marrow cells derived from a patient are
rendered resistant to HIV replication. Development of improved antisense RNA technologies will be
particularly useful to study the mechanism of action of recessive
oncogenes.
StatusFinished
Effective start/end date7/1/896/30/02

Funding

  • National Institutes of Health: $316,174.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $240,656.00
  • National Institutes of Health: $289,343.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $306,965.00
  • National Institutes of Health: $224,809.00
  • National Institutes of Health: $265,816.00
  • National Institutes of Health
  • National Institutes of Health: $234,734.00

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Tars
HIV
Immunization
Antisense RNA
T-Lymphocytes
RNA
Acquired Immunodeficiency Syndrome
Volunteers
Cell Line
Lymphocytes
Transfer RNA
Genes
Bacteriophage T7
RNA Polymerase II
Antisense Oligonucleotides
Therapeutics
Virus Replication
Bone Marrow Cells
Molecular Biology

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)