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Characterization of a mobilization-competent simian immunodeficiency virus (SIV) vector containing a ribozyme against SIV polymerase

Academic Article
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Overview

authors

  • Morris, Kevin
  • Grahn, R. A.
  • Looney, D. J.
  • Pedersen, N. C.

publication date

  • June 2004

journal

  • Journal of General Virology  Journal

abstract

  • Exploitation of the intracellular virus machinery within infected cells to drive an anti-viral gene therapy vector may prove to be a feasible alternative to reducing viral loads or overall virus infectivity while propagating the spread of a therapeutic vector. Using a simian immunodeficiency virus (SIV)-based system, it was shown that the pre-existing retroviral biological machinery within SIV-infected cells can drive the expression of an anti-SIV pol ribozyme and mobilize the vector to transduce neighbouring cells. The anti-SIV pol ribozyme vector was derived from the SIV backbone and contained the 5'- and 3'LTR including transactivation-response, Psi and Rev-responsive elements, thus requiring Tat and Rev and therefore limiting expression to SIV-infected cells. The data presented here show an early reduction in SIV p27 levels in the presence of the anti-SIV pol ribozyme, as well as successful mobilization (vector RNA constituted approximately 17 % of the total virus pool) and spread of the vector containing this ribozyme. These findings provide direct evidence that mobilization of an anti-retroviral SIV gene therapy vector is feasible in the SIV/macaque model.

subject areas

  • Base Sequence
  • Chromatography, High Pressure Liquid
  • Gene Products, pol
  • Genetic Therapy
  • Genetic Vectors
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Catalytic
  • Simian Acquired Immunodeficiency Syndrome
  • Simian Immunodeficiency Virus
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Identity

International Standard Serial Number (ISSN)

  • 0022-1317

Digital Object Identifier (DOI)

  • 10.1099/vir.0.19106.0

PubMed ID

  • 15166433
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Additional Document Info

start page

  • 1489

end page

  • 1496

volume

  • 85

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