Cellular Delivery of Protein Therapeutics for the Treatment of Amyotrophic Lateral Sclerosis Using Endogenous Retroviruses
Abstract
Over 90 percent of Amyotrophic Lateral Sclerosis (ALS) cases are sporadic without a clear initiating molecular event. However, like in many neurodegenerative diseases, protein aggregation and defects in protein degradation are common features in ALS. In 97 percent of patients with ALS, these neuronal protein aggregates include a protein called TAR DNA binding protein-43 (TDP-43). Clearance of neuronal TDP-43 aggregates in experimental models of ALS using intracellular protein therapeutics, such as monoclonal antibodies targeting TDP-43 aggregates for degradation, is associated with increased cell survival and reduced motor defects. In this project we are developing a new cell therapy for the targeted degradation of aggregated TDP43. To date, we have identified the genetic elements required for the efficient delivery of genetically encoded payloads including TDP-43-degrading proteins, stably engineered cells as delivery vehicles and validated this approach using a series of orthogonal in vitro assays. In addition, we have established the required in vivo model and required analytical assays.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2024
- Accession Number
- AD1227980
Entities
People
- Tim Luetkens
Organizations
- University of Maryland, Baltimore