Unmet Need / Invention Novelty: Haploinsufficiency occurs when one gene allele is inactivated and the amount of gene product expressed from the remaining active allele is insufficient for proper gene function. Targeted restoration of mRNA expression and translation may offer a therapeutic window.
Technical Details: Johns Hopkins researchers designed compositions and methods to amplify mRNA translation to treat haploinsufficiencies. The polyA tail attached to the 3’ end of human mRNAs serves as a master regulator of gene expression; however, once in the cytoplasm the polyA tail is gradually removed by deadenylases, therefore acting like a slow burning fuse that dictates how long a single mRNA continues to make protein. Disclosed here is a CRISPR-based system that tethers a positive acting mRNA regulator to bind and remain resident with an mRNA, thereby controlling its extended translation and restoration of protein levels to normal. In-vitro data from a human cell line transfected with the intensifier system, showed the therapy successfully increased expression of the targeted gene on a protein and mRNA level, therefore presenting a promising novel strategy to treat haploinsufficiency disorders.
Value Proposition:
· CRISPR-based mRNA intensifier prolonging mRNA translation to treat haploinsufficiencies
· Targetable to mRNAs of interest
· Easy delivery via viral vector or nanoparticle
· Enables tight regulation of mRNA translation and restoration of desired gene product
Looking for Partners to: Develop & commercialize the technology as a mRNA intensifier restoring mRNA translation to treat haploinsufficiencies
Stage of Development: Pre-Clinical
Data Availability: In-Vitro
