A novel RNA therapeutic for the treatment of CTNNB1 syndrome

Awardee: Jeff Coller

Institution: Johns Hopkins University

Grant Amount: $63,312

Funding Period: February 1, 2025 - January 31, 2026

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Summary:

B-catenin is a protein that is important for proper function and communication between cells of an organism. Involved in cancer, it has also more recently been implicated in neurodevelopmental disorders, including autism. Children with mutations that decrease the levels and thereby affect the function of B-catenin show intellectual disability, microcephaly and developmental delays. We have developed an RNA technology that can enhance the expression of a given protein by increasing its messenger RNA’s potency, by tethering a polyadenosine tail to the transcript via an antisense oligonucleotide. Preliminary results show that this strategy can increase the levels of B-catenin in human neurons, suggesting it could treat patients with different mutations that lead to insufficient B-catenin levels.