Translating Lessons from GalNAc to the Brain Exploring How Oligonucleotide Chemistry Shapes CNS Delivery and Distribution

• Applying key learnings from the GalNAc platform to CNS-targeted delivery systems to improve brain exposure and therapeutic performance
• Understanding how oligonucleotide backbone chemistry, from negatively charged siRNAs to neutral PMOs, influences conjugate design and biodistribution
• Evaluating the impact of drug-to-antibody ratio and conjugation architecture, including 1:1, 4:1 and 8:1 formats, on delivery efficiency and CNS distribution profiles
• Leveraging chemical modifications to optimize shuttle performance, enhance target engagement and overcome barriers to effective brain delivery

Speakers:

Muthiah (Mano) Manoharan

Senior Vice President, Innovation Chemistry & Alnylam Distinguished Scientist

Alnylam Pharmaceuticals