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

Kevin V. Morris, Robert A Grahn, David J. Looney, Niels C Pedersen

Research output: Contribution to journalArticle

4 Scopus citations

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, Ψ 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 ∼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.

Original languageEnglish (US)
Pages (from-to)1489-1496
Number of pages8
JournalJournal of General Virology
Volume85
Issue number6
DOIs
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Immunology
  • Virology

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