RNA-based drugs and vaccines

Abstract

RNA-based approaches have provided novel alternatives for modern drug discovery. The application of RNA as therapeutic agents has, until recently, been hampered by issues related to poor delivery and stability, but chemical modifications and new delivery approaches have increased progress. Moreover, the discovery of the importance of RNA in gene regulation and gene silencing has revealed new drug targets, especially related to treatment of cancer and other diseases. Recent engineering of small molecules designed from RNA sequences to target miRNAs opens up new possibilities in drug development. Furthermore, RNA-based vaccines have been engineered applying RNA virus vectors and non-viral delivery for vaccine development.

Keywords:

• gene silencing
• miRNA
• RNA interference
• RNA-based drugs
• RNA-based vaccines
• viral RNA replicons

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Proof of concept both in vitro and in vivo of siRNA, short hairpin RNA and miRNA with potential therapeutic efficacy.

• Development of nanoparticle and lipid-based technologies for optimized targeted delivery of RNA molecules.

• Design of lead small molecules targeting RNA, specifically miRNA hairpin precursors.

• Application of naked RNA replicons, RNA replicon–lipid nanoparticles complexes and recombinant viral-like particles based on flaviruses and alphaviruses for immunization studies in animal models.

• Immunization with flavivirus and alphavirus RNA replicons provide protection against challenges with lethal doses of viruses and cancer cells in rodents and primates.

• Clinical trials for RNA-based drugs and vaccines in progress.