Engineering Brain-Targeted Therapeutics: Exploring Oligo Payloads, Dual Shuttles, & Human Receptor Expression

• Engineering and benchmarking oligo delivery vehicles and dual-target brain shuttles to optimize transcytosis efficiency and neuronal uptake, while balancing affinity, valency, and receptor trafficking dynamics
• Evaluating modality-specific considerations for dual shuttles including antibody and oligonucleotide payload delivery, and defining engineering principles to enhance target engagement while avoiding rapid plasma clearance, reduced BBB transport or decreased neuronal uptake
• Profiling expression levels of TfR, CD98hc, IGF1R, and emerging BBB targets across human brain microvessels reveals conserved disease-state expression but high inter-individual variability, with potential implications for shuttle-enabled therapeutics

Speakers:

James Gorman

Principal Investigator, Brain Targeting Program

WYSS Institute, Harvard Medical School