Muscle

Our lab is interested in understanding the role of siRNA chemical architecture on pharmacokinetic and pharmacodynamic (PK/PD) properties of siRNA in the muscle following systemic administration. Identification of a hyper-functional lead targeting myostatin has allowed us to investigate how methyl modifications and structure impact efficacy and duration of effect across muscle tissues and in the heart. 

Our lab is also very interested in applying this technology to diseases of muscle and connective tissue. We are collaborating with the Jae-Hyuck Shim Lab in the Department of Medicine to develop multi-functional siRNAs to suppress trauma-induced heterotopic ossification in Fibrodysplasia Ossificans Progressiva (FOP). FOP is a devastating rare disease caused by a monogenic autosomal dominant mutation in ACVR1, leading to heterotopic ossification, or bone growth, following injury and inflammation to the muscle and connective tissue. We have developed a combinatorial siRNA treatment targeting the mutant ACVR1 receptor and an inflammatory target that significantly reduce bone growth after injury in a mouse model of FOP.