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Optimizing regulatable gene expression using adenoviral vectors
Author(s) -
Lee YounBok,
Glover Colin P. J.,
Cosgrave A. Siobhan,
Bienemann Alison,
Uney James B.
Publication year - 2005
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2004.028209
Subject(s) - transgene , woodchuck hepatitis virus , enhancer , biology , gene expression , genetic enhancement , gene , regulation of gene expression , microbiology and biotechnology , vector (molecular biology) , virus , genetics , recombinant dna , hepatitis b virus , hepadnaviridae
Inducible gene expression systems have typically encountered limitations, such as pleitropic effects of the inducer, basal leakiness, toxicity of inducing agents and low levels of expression. However, recently non‐toxic, tightly regulated control of transgene expression has been reported for several systems, the most frequently cited being the tetracycline gene control system. We have found that the individual components of the Tet system [the Tet transactivators and tetracycline responsive element (TRE)] function optimally to control gene expression when they are incorporated into separate adenoviral vectors. Furthermore, incorporation of the Woodchuck hepatitis virus post‐transcriptional enhancer (WPRE) allows a dual vector Tet‐regulatable Ad system to be used at very low titres (2 × 10 4 ) that elicit a minimal inflammatory response, with no loss of transgene expression or ability to regulate transgene expression. This and similar regulatable systems will benefit studies investigating neuronal gene function and those seeking to develop effective neuronal gene therapy strategies.