Day Two

• Analyse biodistribution mechanisms and drivers of liver accumulation
• Modify lipid structure and formulation parameters to shift organ targeting
• Validate targeting strategies in vivo to strengthen translational confidence

• Explore strategies to modulate LNP composition and surface characteristics to enable selective targeting beyond hepatic tissues and improve cell-specific uptake
• Assess emerging approaches to overcome biological barriers, including the blood– brain barrier, to unlock delivery to previously inaccessible tissues
• Evaluate how advances in targeting, biodistribution control and in vivo performance are translating into more effective therapies for complex and hard-to-treat diseases

• Optimise lipid composition and formulation parameters to improve mRNA delivery efficiency, stability and safety
• Tune LNP design to influence biodistribution and enable more precise, cell-specific targeting
• Bridge discovery and clinical translation by aligning LNP design with scalability, manufacturability and regulatory requirements

3–4 speakers each briefly defend a different approach in this open debate. The audience votes on the most promising strategy.

• Lipid chemistry vs formulation tuning vs hybrid systems
• Passive biodistribution control vs active targeting (ligands, peptides, etc.)
• Incremental optimisation vs completely new delivery paradigms
• What actually translates in vivo vs what only works in preclinical models

• Evaluate how LNP design choices impact therapeutic performance in real disease models
• Identify gaps between delivery optimisation and clinical application needs
• Assess how researchers adapt existing LNP platforms for specific therapeutic use cases
• Highlight where current LNP systems fall short from an end-user perspective

• Bypassing accelerated blood clearance by reducing recognition from pre-existing and induced anti-PEG antibodies
• Structural design of PEG-alternatives that maintain nanoparticle stability and endosomal escape while minimising immune detection
• Reviewing in vivo and NHP data demonstrating sustained protein expression and low toxicity across longitudinal dosing cycles

• Applying drug-targeting and immunisation principles to reduce off-target toxicity and improve tolerability of mRNA–LNP vaccines
• Designing formulations and dosing strategies that enable safe repeat administration without diminishing immune response
• Optimising LNP composition and delivery to enhance therapeutic durability and sustain protective efficacy over time

• Evaluate degradation pathways, optimise formulation stability and extend shelf life
• Improve thermostability, reduce cold chain dependency and enable broader distribution
• Align storage conditions with performance requirements and ensure reliability in clinical and commercial settings

• Exploring the design and delivery of inhaled siRNA therapies for targeted, tissue-specific gene silencing
• Overcoming key challenges in pulmonary delivery, stability and efficient cellular uptake
• Translating preclinical innovation into clinical success for precision respiratory therapeutics