Genes can be delivered to patients for the treatment of hereditary disorders and a myriad of multigenic diseases including cancer. This is the basis for gene therapy, expected to transform the health system in the near future. Before these therapies can be widely implemented, it is compulsory to have a technology that sustains the level of the therapeutic gene within the threshold.
- To develop a system that tunes the expression of the therapeutic gene in response to a drug with outstanding benefits for gene therapy and to apply this system to a novel treatment for hepatocellular carcinoma.
Problem to Solve
A perfect gene therapy requires that a single dose of a vector should be enough to cure the disease for the lifetime of the patient. However, once the vector and the therapeutic DNA are inside the cells, they are not susceptible to an external control that tunes the levels of the beneficial gene within the therapeutic window. Ideally, clinicians could adjust expression by changing the dose of a safe drug designed to control the expression of the therapeutic gene. This describes an inducible system. Several inducible systems have been developed but they are deficient for gene therapy.
The team has created ROUTER, an inducible system based on a RNA sequence that, when accessible, interacts with a cellular complex that blocks gene expression. The system reaches inducibility when a given drug binds a riboswitch structure that responds by hiding the complex binding sequence, leading to gene expression.
ROUTER 1.0 is small in size, invisible for the immune system, safe, cell-type independent, displays synergistic effects when multimerized and potent. ROUTER 2.0 will be developed to respond to FDA-approved drugs with no toxicity and excellent bioavailability.