Genetic Rescue of Dystrophic Muscle In Utero

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Despite many successful examples of gene transfer to limited areas of postnatal skeletal muscle, regional or systemic delivery suitable to treat inherited muscle diseases such as Duchenne muscular dystrophy (DMD) has proved elusive. Gene or cell transfer during the fetal stage holds the potential of more efficient and widespread genetic complementation of dystrophin deficiency in DMD. An important rationale to pursue therapeutic strategies for the dystrophic fetus is that muscle stem cells are more plentiful in fetal muscle than in adult muscle. Furthermore, viral vector-mediated gene delivery and engraftment of genetically engineered muscle precursor cells to skeletal muscle may be enhanced during this fetal stage. Therefore, we will explore the feasibility of performing gene and cell transfer to muscle in utero exploiting the benefits of lower tissue mass and immune immaturity of the fetus as well as the earlier stage of muscle development. Specific Aims: 1. To evaluate in utero dystrophin gene delivery using high-capacity adenoviral (HC-Ad) vectors. 2. To evaluate in utero dystrophin gene delivery using adeno-associated viral (AAV) vectors. 3. To evaluate in utero gene delivery using early progenitor myogenic cells