title: Enhancing the utility of adeno-associated virus gene transfer through inducible tissue-specific expression.
abstract: The ability to regulate both the timing and specificity of gene expression mediated by viral vectors will be important in maximizing its utility. We describe the development of an adeno-associated virus (AAV)-based vector with tissue-specific gene regulation, using the ARGENT dimerizer-inducible system. This two-vector system based on AAV serotype 9 consists of one vector encoding a combination of reporter genes from which expression is directed by a ubiquitous, inducible promoter and a second vector encoding transcription factor domains under the control of either a heart- or liver-specific promoter, which are activated with a small molecule. Administration of the vectors via either systemic or intrapericardial injection demonstrated that the vector system is capable of mediating gene expression that is tissue specific, regulatable, and reproducible over induction cycles. Somatic gene transfer in vivo is being considered in therapeutic applications, although its most substantial value will be in basic applications such as target validation and development of animal models.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, PA 19104, USA.
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.forename: Julie
authors.initials: J
authors.lastname: Johnston
authors.forename: Arbans
authors.initials: A
authors.lastname: Sandhu
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Bish
authors.forename: Ruben
authors.initials: R
authors.lastname: Hovhannisyan
authors.forename: Odella
authors.initials: O
authors.lastname: Jno-Charles
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods*
chemical_list: D011994:Recombinant Proteins
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