RNA therapeutics 2.0: Expanding the landscape from mRNA vaccines to splicing modulators and beyond - PubMed
5 days ago
- #RNA therapeutics
- #mRNA vaccines
- #precision medicine
- RNA therapeutics have evolved from first-generation agents like fomivirsen and pegaptanib to more advanced modalities.
- Recent advancements include mRNA vaccines for COVID-19, enabled by improvements in backbone chemistry, nucleoside modifications, and targeted delivery systems like GalNAc conjugation and LNP encapsulation.
- RNA Therapeutics 2.0 offers enhanced stability, tunability, and tissue-specific targeting.
- New methodologies such as circRNAs, saRNAs, splice-switching ASOs, small-molecule splicing modulators, and ADAR-directed base editors are expanding therapeutic applications.
- Applications now extend to oncology, neurology, metabolic diseases, and rare genetic disorders.
- Innovations in delivery systems, including ligand-targeted LNPs, peptide conjugates, and engineered exosomes, are improving extrahepatic delivery.
- AI is accelerating the optimization of RNA sequences, chemistries, and vectors.
- Combining RNA therapeutics with gene therapy enables personalized treatments like n-of-1 medicines.
- The review highlights the transition from early oligonucleotide drugs to a diverse range of RNA platforms, discussing advancements, challenges, and emerging technologies in RNA-based precision medicine.