Inducible long-term gene expression in brain with adeno-associated virus gene transfer

RP Haberman, TJ McCown, RJ Samulski - Gene therapy, 1998 - nature.com
Gene therapy, 1998nature.com
Recombinant adeno-associated virus (rAAV) vectors hold promise for treating a number of
neurological disorders due to the ability to deliver long-term gene expression without toxicity
or immune response. Critical to these endeavors will be controlled expression of the
therapeutic gene in target cells. We have constructed and tested a dual cassette rAAV vector
carrying a reporter gene under the control of the tetracycline-responsive system and the
tetracycline transactivator. Transduction in vitro resulted in stable expression from the vector …
Abstract
Recombinant adeno-associated virus (rAAV) vectors hold promise for treating a number of neurological disorders due to the ability to deliver long-term gene expression without toxicity or immune response. Critical to these endeavors will be controlled expression of the therapeutic gene in target cells. We have constructed and tested a dual cassette rAAV vector carrying a reporter gene under the control of the tetracycline-responsive system and the tetracycline transactivator. Transduction in vitro resulted in stable expression from the vector that can be suppressed 20-fold by tetracycline treatment. In vivo experiments, carried out to 6 weeks, demonstrated that vector-transduced expression is sustained until doxycycline administration upon which reporter gene expression is reduced. Moreover, the suppression of vector-driven expression can be reversed by removal of the drug. These studies demonstrate long-term regulated gene expression from rAAV vectors. This system will provide a valuable approach for controlling vector gene expression both in vitro and in vivo.
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