Pre-Conference Focus Day
Tuesday, March 21

Next-Generation Delivery Methods to Get RNAi Therapeutics Into Extrahepatic Tissues

8:50 am Chair’s Opening Remarks

Comparing Safety & Efficiency of Current Delivery Vehicles to Increase Specificity

9:00 am Panel Discussion – Mapping Out the Landscape of Delivery Modalities


  • What are the pros and cons of current delivery modalities?
  • Comparing peptides, polymers, antibodies, exosomes, and aptamers as delivery vehicles
  • What is understood about their safety and efficacy?
  • How validated are they for each cell type?
  • How to improve the efficiency of delivery to the liver?
  • Comparing the duration of effect across delivery mechanisms
  • Comparing the therapeutic risk-reward profile of each mode of delivery

10:00 am Morning Networking Break

Leveraging Delivery Technologies to Move Beyond Hepatic Tissues

11:00 am Asymmetric siRNA Therapeutics Targeting Skin, Eye, & Liver Diseases

  • Dong-ki Lee Founder & Chief Executive Officer, OliX Pharmaceuticals


  • RNAi therapeutics have the potential to target hepatic as well as extra-hepatic diseases with the use of optimal delivery methods.
  • We have established lipid-conjugated asymmetric siRNA (asiRNA) targeting skin and ocular tissues to develop therapeutic programs against the hypertrophic scar, androgenic alopecia, and age-related macular degeneration.
  • We also present a GalNAc-based liver targeting strategy to tackle diseases such as HBV and NASH

11:30 am Centyrin Platform, a Novel Strategy for Extrahepatic Delivery of siRNA

  • Yao Xin Principal Investigator, Aro Biotherapeutics


  • Centyrins as drug delivery scaffold
  • ARO Centyrin-siRNA platform and lead characterization
  • Overview of preclinical progress

12:00 pm Networking Lunch

Optimizing Delivery Into the CNS for Robust Silencing

1:00 pm Intravenous CNS Delivery of siRNA Using SAMiRNA Platform


  • Cover various targeting strategies for targeting the blood-brain barrier, but also additional challenges of siRNA delivery such as metabolic clearances and endosomal escape
  • Benefits of SAMiRNA platform
  • PoC safety and efficacy data showing effective knockdown using SAMiRNA

1:30 pm Dissecting the Impact of Chemistry & Structure on siRNA Activity in the CNS

  • Julia Alterman Assistant Professor, University of Massachusetts Medical School


  • Impact of phosphorothioate backbone modifications on siRNA accumulation and distribution in mice and sheep brains
  • Impact of linker chemistry on siRNA accumulation and distribution in the mouse brain
  • Dual targeting, multivalent siRNAs exhibit robust silencing of two genes in mouse brain

2:00 pm Round Table Discussion: Next-Generation Delivery Approaches

  • Jihye Park Associate Director, Dicerna TRU of Novo Nordisk


  • What can be learned from first-generation delivery to inform next-generation approaches?
  • Comparing the conjugation process with LNP formulation
  • Towards the Holy Grail; discovery technology that is as effective as GalNac in the liver, in extrahepatic tissues
  • Assessing IV, inhalation, and oral administration

3:00 pm Networking Break

Shining a Spotlight on Strategies That Increase Endosomal Escape

3:30 pm Modified Pore Forming Peptides for Self-Assembling RNA Nanoparticle Formation & Optimized Endosomal Escape


  • Altamira’s OligoPhore and SemaPhore platforms rapidly condense any RNA into <100 nm polyplexes that are taken up by cellular macropinocytosis
  • The peptide polyplexes avoid hepatic sequestration after systemic administration, and penetrate inflamed disease microenvironments by the “endothelial permeability and retention” (EPR) mechanism
  • Endosomal pH-dependent polyplex disassembly releases the peptide to permeabilize the endosomal membrane for rapid and extensive release of siRNA or mRNA into the cytoplasm to target protein production in vivo in multiple disease categories

4:00 pm Tools for Understanding Endosomal Escape for Nucleic Acid Delivery


  • What in vitro methods have been explored for understanding endosomal escape?
  • What methodologies are available to monitor the siRNA in the body?
  • What do we understand about different platforms and methods of cytosolic delivery?

4:30 pm End of Pre-Conference Focus Day