AAV-LICA1-Sensor-Decoy

AAV-LICA1-Sensor-Decoy is an investigational adeno-associated virus (AAV)-based gene therapy designed for the treatment of myotonic dystrophy type 1 (DM1). The therapy utilizes an engineered, muscle-tropic AAV capsid called LICA1, which is computationally designed to target integrin alphaV-beta6 (αVβ6) on skeletal muscle cells while detargeting the liver, thereby allowing for lower therapeutic doses and reduced systemic toxicity. AAV-LICA1 delivers a 'Sensor-Decoy' transgene cassette. The 'Decoy' component is an engineered RNA-binding protein with high affinity for expanded CUG repeats (CUGexp-RNA), which acts to release sequestered endogenous Muscleblind-like protein 1 (MBNL1) from nuclear foci and restore its normal splicing regulation function. The 'Sensor' component is a splice-sensor system that autoregulates the expression of the Decoy protein based on the level of MBNL activity in the affected muscle cells. This gene therapy is being developed by Genethon in collaboration with Sorbonne Université, Inserm, and the Institut de Myologie.