Extracellular Vesicles as Therapeutic Vehicles for Myotonic Dystrophy
Abstract
Topic Area: Myotonic Dystrophy Area of Encouragement: Development and/or testing of novel and/or innovative treatments, including those utilizing gene editing or silencing. Central Critical Problem or Question to Be Addressed: Myotonic dystrophy (DM) is the most common muscular dystrophy in adults, affecting ~1:8000 worldwide. DM is an inherited condition with no cure or effective treatment. DM type 1 (DM1) results from a change in the DNA of a gene called DMPK. DM1 patients develop progressive muscle weakness, dysfunction of the heart, and excessive fatigue. Development of effective therapies for DM is a major unmet need. Recently, a new technology has become available that enables corrective changes in the DNA of genes that can have therapeutic benefit. One of these approaches is called CRISPR/Cas9 and has shown promise for treatment of DM1 using cells in a dish and a mouse model. To make this therapeutic approach viable for DM1 patients will require use of a gene therapy tool known as an adeno-associated viral (AAV) vector to deliver, or carry, the CRISPR/Cas9 gene to muscle fibers. Sometimes a person’s immune system can make gene therapy difficult by attacking the AAV vector, thereby reducing the delivery of the therapeutic gene. A method that enhances delivery of AAV to muscle tissue and that is resistant to the immune system is needed. Innovation of the Idea: This project will use a novel method to increase the efficiency of AAV gene therapy in muscle tissue of DM1 mice by the use of small vesicles or “bubble-like” structures that contain the AAV and serve to protect the AAV and its cargo from the immune system. These AAV-containing vesicles have shown superior delivery of genes in non-muscle tissue of healthy mice compared to the standard method of AAV gene therapy without vesicles. Development of AAV-containing vesicles that carry CRISPR/Cas9 for the treatment of DM1 will be a new venture. Ultimate Applicability and Impact of the Research: This novel gene therapy technology has the potential to benefit all DM patients. If successful, this approach could be extended more broadly beyond DM as a novel drug delivery/gene transfer platform for other muscular dystrophies or inherited conditions that would benefit from gene therapy.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010145
Entities
People
- Thurman Wheeler
Organizations
- Massachusetts General Hospital
- United States Army