Dimerizer-regulated gene expression.
Control of gene expression using small molecules is a powerful research tool and has clinical utility in the context of regulated gene therapy. Use of chemical inducers of dimerization, or dimerizers, for this purpose has several advantages, including tight regulation, modularity to facilitate iterative improvements, and assembly from human proteins to minimize immune responses in clinical applications. Recent developments include the use of the rapamycin-based dimerizer system to regulate the expression of endogenous genes, the generation of new chemical dimerizers based on FK506, dexamethasone and methotrexate, and progress towards the clinical use of adeno-associated virus and adenovirus vectors regulated by rapamycin analogs.
Pollock
Roy
R
ARIAD Gene Therapeutics, 26 Landsdowne Street, Cambridge, MA 02139, USA. roy.pollock@ariad.com
Clackson
Tim
T
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000737:chemistry*; D000229:Dependovirus / Q000235:genetics; D003907:Dexamethasone / Q000378:metabolism; D019281:Dimerization; D005786:Gene Expression Regulation / Q000187:drug effects*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008727:Methotrexate / Q000378:metabolism; D051379:Mice; D017853:Phosphotransferases (Alcohol Group Acceptor); D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020123:Sirolimus / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases; D014158:Transcription, Genetic; D014162:Transfection
D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; D003907:Dexamethasone; D004247:DNA; D017853:Phosphotransferases (Alcohol Group Acceptor); C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D008727:Methotrexate