Development of a cDNA/mRNA Delivery System Utilizing Ophidion’s CNS Carrier Technology to Treat Rett Syndrome
All of the curative approaches that RSRT is pursuing will require the delivery of therapeutics into as many brain cells as possible. The current delivery method of choice for neurological disorders is AAV9, a viral vector that no longer contains the viral DNA and instead delivers a therapeutic cargo. The safety profile of AAV9 is very good and does not cause illness in humans, but current challenges as a delivery vehicle include limited distribution in the brain, limited size of cargo that can be accommodated, initiation of an immune response upon repeat dosing (though a large effort to eliminate immunity is underway in the field), and difficult and expensive manufacturing.
For these reasons RSRT has been exploring a number of non-viral delivery options to overcome AAV9 challenges. The biotech company, Ophidion, has developed a novel peptide carrier technology called OCCT to deliver large cargo such as RNA and DNA to the brain via intravenous injection.
The goal of the project is to achieve delivery of MECP2 RNA or DNA broadly across the brain after intravenous delivery. RSRT is taking a milestone driven approach to fund the first milestone to achieve the delivery of the MECP2 gene in neurons grown in the lab. Once this milestone is achieved the next step would be to deliver the gene to the brain in an animal model of Rett.