Characterization of a mobilization-competent simian immunodeficiency virus (SIV) vector containing a ribozyme against SIV polymerase.
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.
Morris
Kevin V
KV
Department of Medicine, Stein Clinical Research Building Room 402, University of California San Diego, La Jolla, CA 92093-0665, USA.
Grahn
Robert A
RA
Department of Population Health and Reproduction, Tupper Hall Room 1114, University of California Davis, Davis, CA 95616, USA.
Looney
David J
DJ
Department of Medicine, Stein Clinical Research Building Room 402, University of California San Diego, La Jolla, CA 92093-0665, USA.
Pedersen
Niels C
NC
Department of Veterinary Medicine and Epidemiology, Tupper Hall Room 2108, University of California Davis, Davis, CA 95616, USA.
D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D015684:Gene Products, pol / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016337:RNA, Catalytic / Q000502:physiology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000628:therapy*; D015302:Simian Immunodeficiency Virus / Q000235:genetics*
D015684:Gene Products, pol; D016337:RNA, Catalytic