A System For Dosage-independent Control of Mecp2 Expression in Rett Syndrome Gene Therapy

Michael Elowitz, PhD | Caltech

$197,681 AWARDED

One of the challenges with gene therapy protein replacement strategies is the potential for production of too much MeCP2 protein. Different levels of gene dosages can come from the fact that some cells will take up more virus and make more MeCP2 protein than others during gene therapy dosing. What if we could design a feedback circuit with a failsafe switch that destroys excess amounts of MeCP2? Based on “feedback circuits” found in nature, the Elowitz team has developed synthetic circuits that can react to and regulate levels of MeCP2. In other words, the circuit can see when there are higher levels of MeCP2 than are needed and get rid of the excess. Regardless of level of gene dosages, the circuit can maintain a relatively fixed level of MeCP2. These circuits will ensure that no matter how many copies of a MECP2 gene are delivered, the right amount of MeCP2 protein will be expressed in the cell.

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