mRNA delivery technologies: Toward clinical translation

Area of Science:

• Biotechnology and Nanomedicine
• Drug Delivery Systems
• Molecular Therapeutics

Background:

• Messenger RNA (mRNA) therapies have achieved significant clinical milestones with the first marketed products.
• Chemical modifications enhance mRNA for clinical use, but effective delivery systems are crucial.
• mRNA nanomedicines must protect the nucleic acid and overcome biological barriers.

Purpose of the Study:

• To provide an overview of mRNA delivery technologies, focusing on lipid nanoparticles (LNPs).
• To highlight recent advances in the clinical applications of mRNA nanomedicines.
• To discuss the role of mRNA therapies in immunotherapy, protein replacement, gene editing, and regenerative medicine.

Main Methods:

• Review of current mRNA delivery technologies, including polymers, polypeptides, and cationic lipids.
• Emphasis on lipid nanoparticles (LNPs) as the most advanced delivery system.
• Analysis of clinical trial data and regulatory approvals for mRNA-based therapeutics.

Main Results:

• Lipid nanoparticles (LNPs) are at the forefront of preclinical and clinical evaluation across various fields.
• Liposomes represent the mRNA delivery technology with the highest clinical translation among LNPs.
• The first regulatory approvals for mRNA products are LNP-based vaccines against COVID-19.
• Clinical translation for cancer focuses on vaccination, engineered CARs/TCRs, and immunomodulators.

Conclusions:

• mRNA nanomedicines, particularly LNP-based formulations, are driving innovation in infectious disease vaccines and cancer immunotherapy.
• Liposomes and exosome-based delivery systems show promise for protein replacement therapy.
• The clinical success of mRNA therapies is rapidly expanding into diverse therapeutic areas.