Gene therapy
Gene therapy involves the introduction of a gene, in our application a gene encoding for the production of GPR139, into the patient with the goal of causing the patient’s body to manufacture more GPR139. This additional GPR139 will be localized in the cells where GPR139 naturally resides and functions, namely the habenular cells of the central nervous system. The company believes that the habenular cells, fortified with this additional GPR139, will be extra responsive to activation by a pharmaceutical agonist (activator) of GPR139.
We have applied for intellectual property protection for both the GPR139 gene therapy and for combination therapy employing gene therapy and pharmaceutical activation. We are testing the applicability of the novel AAV6.2FF gene delivery platform for mediating efficient neuroprotector transgene expression in the brain. Specifically, we will evaluate expression of the CNS G protein-coupled receptor, GPR139, the dopamine receptor, DRD1A, as well as the serotonin receptor, 5-hydroxytryptamine receptor 4 (5HTR4).
The specific objectives of this project are to:
- Synthesize codon and RNA optimized GPR139, DRD1A, and 5HTR4;
- Insert these three neuroreceptor genes into AAV vectors;
- Perform Western blots to demonstrate the constructs are functional and the proteins are expressed properly;
- Produce high titer AAV vectors expressing GPR139, DRD1A, and 5HTR4;
- Administer the AAV vectors to mice via the intravenous and intracranial routes; and
- Visualize and quantify neuroreceptor gene expression in the brain, liver, lung, heart, kidney, and spleen following intravenous delivery; and
- Visualize and quantify neuroreceptor gene expression in the brain only following intracranial delivery.
