Pink Floyd's "Another Brick in the Wall" increased mRNA delivery to mouse brains by 10x

Key Findings

🦠 New COVID Vaccine Shows Superior Performance

• DS-5670d vaccine achieved 87.3% immune response rates compared to 82.9% for Pfizer's current vaccine in 725 participants

• The vaccine worked effectively across all age groups and immune histories—even in people who were never vaccinated or infected before

• No major safety differences were observed between the new vaccine and the established Pfizer vaccine

🧬 Computer-Designed Vaccines Outperform Traditional Approaches

• mRNA vaccines encoding computer-designed protein nanoparticles elicited 5- to 28-fold higher neutralizing antibodies than current spike protein vaccines in mice

• The nanoparticles displayed 60 copies of viral antigens in an optimized array, mimicking natural virus structure

• Mice were completely protected from both original COVID strain and Omicron BA.5 variant after vaccination

🎯 New Lipid Design Reduces Liver Accumulation

• Novel ionizable cholesteryl lipids reduced liver uptake of mRNA by decreasing binding to ApoE proteins that normally target the liver

• The three-component system improved spleen delivery compared to standard four-component lipid nanoparticles

• Computer modeling (DiffDock-L) successfully predicted which lipid designs would avoid liver targeting

🔬 HIV Vaccine Strategy Shows Promise Against Multiple Targets

• Simultaneous delivery of four different mRNA vaccines activated precursor cells for four distinct HIV antibody types without competition between them

• mRNA delivery outperformed protein-based vaccines in driving immune cell maturation across different doses and precursor frequencies

• The approach worked even when targeting multiple different sites on the HIV virus envelope simultaneously

🧪 mRNA Modification Prevents Cellular Stress Response

• N1-methylpseudouridine modification of mRNA prevented cell death and improved protein production in early zebrafish embryos

• The modification reduced binding to Prkra, a sensor protein that normally triggers cellular stress responses to foreign RNA

• Modified mRNAs showed significantly better performance in pluripotent cells compared to unmodified versions

❄️ Breakthrough in mRNA Storage Stability

• Adding recombinant ApoE3 protein plus 10% sucrose preserved >90% of mRNA activity after 4 weeks at -80°C and three freeze-thaw cycles

• Treated samples retained >70% potency for 72 hours at room temperature, far exceeding the ≤12 hour window of current COVID vaccines

• The approach increased liver expression ~3-fold in mice without causing toxicity or inflammation