• Strategies for understanding and mitigating immune responses that result in safety issues and/or interfere with intended mechanism of action
  • Modifying nucleic acid sequences or their chemical structures to reduce immunogenicity
• Addressing safety and toxicity issues —particularly related to accumulation of delivery vehicles at high dosages
• Moving towards standardized approaches to characterizing the pharmacological and toxicological profiles of nucleic acids
• Assessing the pros and cons of preclinical models for assessing nucleic acids
• Exploring the latest tools for understanding distribution and clearance
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

• Are manufacturing challenges around sustainability and scalability holding the oligonucleotide field back from reaching its full potential?
  • How is the field addressing scale-up difficulties, high solvent consumption, and increasing environmental impact concerns?
  • How suited are different synthesis options (including solid-phase, liquid-phase, enzymatic manufacturing and hybrid approaches) to solving these issues?
• Exploring the latest tools and strategies for producing large quantities of mRNA and oligonucleotides (e.g., aptamers) at scale and with high purity, fidelity, and consistency
• Improving the connection between upstream and downstream processes
• Are traditional synthesis options holding the oligonucleotide field back from reaching its full potential?
• Dissecting the pros and cons of synthetic versus plasmid DNA for therapeutic and manufacturing applications
• Current issues with cost and variability of raw materials

• Structural modifications to enhance stability and translation efficiency
• In vivo stability and pharmacokinetics of oligonucleotides (aptamers, RNA-based modalities)
• Tools and approaches to gain mechanistic insights into stability and degradation of nucleic acids and LNPs?
• Approaches for improving the stability of DNA nanostructures 
• Formulation optimization to improve stability and release kinetics of nanoparticles, and non-temperature-dependent formulations
  
  
  
  
  
  
  
  
  
  

• Are existing oligonucleotide purification tools up to the challenge of meeting regulators’ expectations 
• How and where are cutting-edge analytics driving downstream process improvements in terms of scalability, speed, cost, and accuracy?
• Enhancing the characterization of complex impurity profiles and removal of product- and process-related impurities (e.g., dsRNA)
• Addressing fill-finish challenges for nucleic acid therapeutics
• Progress in advancing non-temperature dependent formulations for mRNA
  
  
  
  
  
  
  

• Troubleshooting nucleic acid therapeutic raw and starting material sourcing strategy’
• How can variability in analysis and quality from different raw material suppliers be addressed?  
  • Addressing the need for standardization 
• Solutions to address the high cost and supply bottleneck of materials and reagents for oligonucleotide manufacturing, and their environmental impact (e.g. liquid phase manufacture, solvent reuse)
• Ensuring a secure and reliable supply chain for pDNA biomanufacturing— how can the space manage potential disruptions in raw materials supply and ensure traceability?
• Understanding regulatory expectations around raw and starting materials for complex nucleic acid products

Oligonucleotides
Analytics

• How are the analytical technology needs of the oligonucleotides space changing in response to regulatory evolution and advances in R&D and manufacturing?

mRNA
Downstream processing and purification

• Exploring opportunities and challenges presented by the purification and analytical toolkits for upscaling and optimizing downstream mRNA production

DNA
Cell-free/synthetic DNA

• Addressing outstanding questions and challenges around synthetic DNA as a raw/starting material and/or a drug substance
  
  
  
  

mRNA
Stability

• Assessing progress in designing 
  and optimizing stable and 
  non-temperature-dependent formulations
  
  
  
  

Oligonucleotides
Sustainability (NEW!)

• The sustainability, availability and environmental impact of materials and reagents remains a key challenge for the space – how can oligonucleotide manufacturing be made greener?

DNA
Plasmid DNA

• What are the current design, production, and supply challenges for pDNA starting material?
  
  
  
  

mRNA
Preclinical and 
translational models

• Which preclinical and translational models are most representative when assessing the safety, stability, and efficacy of mRNA?

Oligonucleotides
Scalability

• Removing key barriers to large-scale RNA and DNA synthesis