mRNA Technology Newsletter
Issue #3September 22, 20257 studies

mRNA vaccines show promise for cancer and rare diseases, while new LNP designs tackle inflammation

This week brought exciting developments in mRNA therapeutics, from cancer vaccines that work alongside checkpoint inhibitors to new delivery systems that could reduce side effects. Plus, researchers are finding ways to make these treatments work better in hard-to-reach tissues.

🎯 Cancer vaccine combines mRNA with immune checkpoint therapy

  • Researchers developed an mRNA vaccine targeting HPV16/18 proteins (which drive many head and neck and cervical cancers) and tested it in mouse tumor models

  • The vaccine alone showed dose-dependent tumor shrinkage, but combining it with anti-PD-1 checkpoint inhibitor led to complete tumor elimination in both HPV16 and HPV18 tumor models

  • The combination therapy expanded HPV-specific CD8+ T cells and increased their infiltration into tumors, suggesting the mRNA vaccine primes the immune system for the checkpoint inhibitor to work more effectively

Why it matters: This approach could offer new treatment options for the 600,000+ people diagnosed annually with HPV-related cancers, particularly since it works by training the immune system to recognize mutated viral proteins that can't harm healthy cells.

🥈 Top 2% journal 🔗 Journal for immunotherapy of cancer 🗓️ Sep 18

Key Findings

🧬 New lipid design reduces mRNA vaccine inflammation

  • Scientists created lipid nanoparticles using lipoic acid (an antioxidant) that delivered mRNA while scavenging harmful reactive oxygen species

  • These particles showed superior mRNA translation and reduced inflammatory cytokine production compared to standard formulations in lab tests

  • When applied to mouse skin for psoriasis gene editing, the new particles successfully edited the CD93 gene and improved disease symptoms through reduced inflammation

💡 Antioxidant-enhanced delivery systems may help reduce the inflammatory side effects that limit repeated mRNA treatments.
🥇 Top 1% journal 🔗 Journal of the American Chemical Society 🗓️ Sep 15

🔬 Crosslinked nanoparticles boost mRNA stability

  • Researchers developed a method to chemically crosslink lipid nanoparticles after assembly, creating more structurally stable delivery vehicles

  • The crosslinked particles showed improved performance under storage conditions and better endosomal escape (getting mRNA out of cellular compartments and into the cytoplasm where it works)

  • Both lab and animal studies demonstrated enhanced mRNA delivery efficiency compared to standard formulations

💡 Better particle stability could enable mRNA medicines to be stored more easily and work more effectively in patients.

🎯 Lung-targeting particles deliver cancer immunotherapy

  • Scientists engineered lipid nanoparticles with a lung-targeting peptide to deliver STING pathway mRNA (which activates immune responses) specifically to lung tissue

  • In mouse models of lung cancer metastasis, the targeted particles dramatically reduced tumor spread and showed no organ toxicity

  • Combining with anti-PD1 therapy achieved near-complete metastasis prevention, driven by increased CD8+ T cell and M1 macrophage infiltration

💡 Tissue-specific targeting may allow powerful immunotherapies to work where needed while avoiding systemic side effects.
🥈 Top 2% journal 🔗 Small (Weinheim an der Bergstrasse, Germany) 🗓️ Sep 15

🧪 Circular RNA vaccines outperform standard mRNA

  • Researchers developed COVID-19 vaccines using circular RNA (which forms a closed loop structure) instead of linear mRNA, delivered via optimized lipid nanoparticles

  • In mice, circular RNA vaccines generated 3.8-fold higher antibody levels and stronger T-cell responses compared to traditional mRNA vaccines

  • The circular structure provides enhanced stability and potentially reduced immunogenicity while maintaining strong immune activation

💡 More stable RNA structures could lead to longer-lasting vaccines that need fewer booster shots.

🔬 Protein delivery beats mRNA for gene editing

  • Scientists compared delivering CRISPR-Cas9 as protein versus mRNA using lipid nanoparticles for correcting cystic fibrosis mutations

  • Cas9 protein delivery outperformed mRNA delivery in both lab studies and live animal lung editing experiments

  • The protein approach achieved more efficient gene correction and better functional recovery of the CFTR protein that's defective in cystic fibrosis

💡 For precise gene editing applications, delivering the editing tool directly as protein may work better than instructing cells to make it from mRNA.
🥉 Top 5% journal 🔗 Nano letters 🗓️ Sep 17

🧬 RSV vaccine proves safe in young children

  • A phase 1 trial tested Moderna's mRNA-1345 RSV vaccine in 46 children aged 12-59 months, with three doses given 56 days apart

  • The vaccine was well-tolerated with mostly mild side effects, and a single injection boosted RSV antibody levels 18.9-fold for RSV-A and 7.2-fold for RSV-B in the lower dose group

  • No serious adverse events occurred during 12 months of follow-up, while three RSV infections were reported among placebo recipients

💡 mRNA vaccine technology may soon expand beyond COVID-19 to protect young children from other respiratory viruses.
Top 20% journal 🔗 Human Vaccines and Immunotherapeutics 🗓️ Sep 14

Implications

These studies suggest mRNA therapeutics are expanding beyond infectious diseases into cancer treatment, rare genetic disorders, and precision medicine. The focus on reducing inflammation and improving targeting could address current limitations that prevent repeated dosing and limit efficacy.

Studies in this issue

Primary sources used for this newsletter.

  1. Mutant HPV16/18 mRNA vaccines trigger targeted T-cell responses and work with anti-PD-1 therapy to shrink tumors in mice
    main storyJournal for immunotherapy of cancer2025-09-18PMID 40967673
  2. Safety and immune response of an mRNA RSV vaccine in children aged 12-59 months with prior RSV exposure
    key findingHuman vaccines & immunotherapeutics2025-09-15PMID 40953212
  3. Using Special Lipid Nanoparticles to Deliver mRNA Through the Skin for Gene Therapy
    key findingJournal of the American Chemical Society2025-09-15PMID 40947594
  4. Cas9 Protein Works Better Than mRNA for Lipid Nanoparticle Delivery in Fixing CFTR
    key findingNano letters2025-09-17PMID 40961329
  5. Lung-Targeted STING mRNA Nanoparticles Slow Tumor Growth and Boost Body-Wide Anti-Cancer Immunity in Non-Small Cell Lung Cancer
    key findingSmall (Weinheim an der Bergstrasse, Germany)2025-09-15PMID 40948207
  6. Crosslinking lipid nanoparticles improves how well mRNA vaccines are delivered and work
    key findingbioRxiv : the preprint server for biology2025-09-18PMID 40964266
  7. Circular RNA vaccine delivered by fat nanoparticles against COVID-19
    key findingProceedings of the National Academy of Sciences of the United States of America2025-09-15PMID 40953267

Continue reading

All mRNA Technology issues