Optimization of an Antisense OligonucleotideHNRNPH2Therapy

National Center For Advancing Translational Sciences

Investigators

Abstract

Prior work supported by the collaborators at the To Cure a Rose (TCAR) Foundation tested seven different ASO designs to determine whether these scaffolds could knock down HNRNPH2 expression with a reciprocal increase of HNRNPH1 expression. Several ASOs showed the desired reciprocal increase in HNRNPH1, and these ASOs were then tested in humanized mouse models to evaluate efficacy and toxicity. In this collaboration, in vitro brain organoids are being developed to support further characterization of the candidate ASOs. To date, several HNRNPH2 iPSCs and control cell lines have been developed and characterized. These HNRNPH2 iPSCs were subsequently differentiated into neuronal stem cells, neurons, and brain organoids. Multiple ASOs were then evaluated for efficacy in both the iPSCs and organoids. The determination of the lead ASO candidate is currently in process.