Precision RNAi for Fibrodysplasia Ossificans Progressiva: a combinatorial, unimolecular, allele selective approach.

we report the development of disease-modifying, allele-selective small interfering RNA (siRNA) targeting ACVR1R206H.When conjugated to docosanoic acid (DCA), administration of the fully modified ACVR1 siRNA, either alone or in combination with an siRNA targeting IL1B (a key regulator of inflammation), results in profound reduction of HO using both responsive (post-trauma) and preventative (pre-trauma) intervention strategies in a murine FOP model.

Notably, the combination therapy outperforms modulation of either target alone.