On the other hand, since autosomal dominant, heterozygous mutation in ACVR1R206H (c.617G>A;p.R206H) causes FOP [6,31], our gene therapy approach was designed to replace the mutant ACVR1R206H receptor with the healthy ACVR1 receptor via the combination approach: (1) the silencing of the expression of the ACVR1R206H receptor at the mRNA level using ACVR1R206H allele-specific amiR and (2) the dilution of aberrant BMP-Smad1/5 signaling by the mutant ACVR1R206H receptor with the codon-optimized WT ACVR1 receptor. This evidence concerns the gene SMAD1 and fibrodysplasia ossificans progressiva.