TFR1 Targeting

Overview

Delivery strategy exploiting transferrin receptor 1's ubiquitous expression on muscle, cardiac tissue, BBB endothelium, and CNS neurons to shuttle oligonucleotide conjugates into cells via receptor-mediated endocytosis. TFR1 (transferrin receptor 1) is expressed on virtually all iron-requiring cells including skeletal muscle, cardiac muscle, blood-brain barrier endothelium, and CNS neurons, making it an ideal pan-tissue target for oligonucleotide conjugate delivery to neuromuscular and CNS disease targets. Full monoclonal antibodies targeting TFR1 cause dose-limiting anemia by crosslinking and blocking the receptor for extended periods; using a Fab fragment with carefully selected epitope affinity enables a hit-and-run mechanism that avoids this toxicity. (Segment 4 (15:00-20:00))