Introduction

As 2024 draws to a close, we’re taking a moment to reflect on an incredible year in RNA science and innovation. From groundbreaking discoveries in RNA biology, to another Nobel Prize celebrating RNA research, and the emergence of transformative RNA-based therapies; 2024 has been nothing short of remarkable. In this eBlog, we are excited to share some of the year’s most impactful highlights in RNA. 

Groundbreaking discoveries into RNA biology

For the second year in a row, research into RNA has led to the Nobel Prize in Physiology or Medicine. This year it was awarded to Victor Ambros and Gary Ruvkun for their discovery of microRNAs (miRNAs)¹. Their research led to a fundamental shift in our understanding of how genes are regulated and has formed the basis of exciting advancements in therapeutic development. 

This year, RNA researchers discovered new aspects of RNA biology and developed novel AI-based algorithms to support future research: 

• Zhu et al. have discovered that specific tRNAs can lead to RNA degradation, providing a new link between translation and stability².
• Shen et al. have developed an improved AI model for predicting the 3D structure of RNA, which can be used to develop better inform drug design³. 
• Zhang et al. have shown how small RNAs (cityRNAs) can associate with AGO3 to silence genes, revealing a separate network for gene regulation than traditional miRNAs⁴.

This year also saw several notable advancements in the understanding of RNA biology and drug activity using our technologies: 

• Haag et al. used m6A-eCLIP to examine methylation patterns in macrophages, revealing a post-transcriptional regulation of TNF⁵. 
• Karginov et al. used RBP-eCLIP to determine how the protein TRA2β promotes the alternative splicing of T cell receptor stimulated genes⁶. 
• Fraire et al. used miR-eCLIP to examine the role of miRNAs in the formation of brain tumors⁷. 
• Shah et al. used eSHAPE to map exactly where a splice modulating small molecule bound to its target RNA, providing key insights into the drug’s mechanism of action⁸.  

New advancements in RNA-based and RNA-targeting medicines

RNA drug development achieved significant milestones in 2024, spanning pre-clinical innovation, promising clinical trials, and new FDA approvals. Below is a snapshot of some of those milestones: 

• Carisma Therapeutics and Moderna: developed chimeric antigen receptor macrophages (CAR-M) programmed with mRNA/LNP technology while still in the body. These CAR-M cells, equipped with glypican-3 (GPC3) antigen, target and destroy cancer cells while sparing healthy tissue. This novel approach offers a promising, new strategy for generating “off-the–shelf" cell therapies targeting solid tumors⁹. 
• Elicio Therapeutics: conducted Phase 1 trials of their mRNA vaccine, ELI-002, designed to address KRAS mutations in pancreatic and colorectal cancers. Results from a Phase 1 trial involving 50 patients showed a 56-fold increase in tumor-targeting T cells and an 86% reduction in cancer progression risk among responsive patients over a six-month period. This highlights mRNA’s potential to treat solid tumors resistant to traditional therapies¹⁰. 
• Moderna’s mRESVIA: approved in May for preventing respiratory syncytial virus (RSV) in adults. This underscores mRNA’s adaptability in tackling infectious diseases and sets the stage for broader applications in vaccine development, such as personalized cancer vaccines, rapid-response vaccines for emerging pathogens, and potential treatments for autoimmune diseases¹¹. 
• Geron’s Imetelstat (Rytelo): approved in June for myelodysplastic syndromes (MDS). This 13-mer oligonucleotide inhibits telomerase activity, addressing aberrant cell proliferation in MDS and offering a new treatment avenue for hematological disorders¹². 

These advancements demonstrate RNA’s expanding role in modern medicine. From cancer immunotherapy to precision vaccines, RNA-based approaches are paving the way for safer, more effective, highly targeted treatments. 

Advancing RNA success at Eclipsebio

At Eclipsebio, our mission is to help our partners achieve research and drug development success through cutting-edge technologies paired with advanced analytics. This year we advanced our mission with the launches of: 

• eSENSE dsRNA: one of the major challenges our partners face when developing RNA-based vaccines and therapies is the presence of double-stranded RNA (dsRNA) contaminants. To help our partners overcome the limitations of current characterization assays, our team has developed a novel sequencing-based approach, eSENSE dsRNA. eSENSE dsRNA provides information on the levels and identity of dsRNA contaminants, helping our partners to more effectively characterize and optimize their RNA-based therapeutics. 
• eMERGE: this year we have expanded our support for making RNA-based medicines through the launch of eMERGE. eMERGE is a comprehensive platform for sequencing-based characterization and optimization of RNA vaccines and therapies. It provides actionable insights into the critical quality attributes that can make the difference between clinical trial success and failure. It has been exciting to see its rapid adoption by leading biopharmas and biotechs. 

Looking forward to 2025

As we look towards 2025, the future looks bright for RNA: 

• We expect that RNA-based medicines will continue to show success, especially as new in vivo therapies are developed for protein replacement and gene editing.  
• We are excited for the rapid increase in AI-driven drug success for RNA sequence optimization and the development of oligonucleotide and small molecule therapeutics. We look forward to supporting their development through our first-in-class AI-ready datasets. 
• RNA biology researchers will continue to make advances into our fundamental understanding of RNA behavior across cells and tissues. 

From everyone at Eclipsebio, thank you to our partners and the larger RNA community for an amazing 2024 and we look forward to supporting you in 2025. 

References

1. Nobel Assembly 
2. Zhu et al.  
3. Shen et al. 
4. Zhang et al. 
5. Haag et al.  
6. Karginov et al. 
7. Fraire et al. 
8. Shah et al. 
9. Bagashev et al. 
10. Pant et al. 
11. FDA BLA Approvals 
12. FDA Novel Drug Approvals