The need to accelerate vaccine development has never been more important as we continue to navigate life amidst a global pandemic. The approval of the first COVID-19 vaccines was an enormous milestone for messenger RNA (mRNA) therapeutics that altered the course of the pandemic and highlights the rapid response potential of the technology. While it may seem as though the mRNA technology underlying the vaccines was an overnight success, it was based on decades of scientific research and innovation, making synthetic RNA safe for injection. However, getting these highly sensitive RNA molecules into cells without degradation while maintaining safety, potency and efficacy was a major challenge. Lipid nanoparticles (LNPs) have solved many of these problems and are now the key to making mRNA vaccines a reality. The demonstrated clinical efficacy of the COVID-19 mRNA vaccines has driven explosive growth in the development of RNA-based vaccines and concomitantly propelled LNPs into the mainstream as an effective drug carrier for complex polynucleotide- and peptide-based therapeutics.
The LNPs used in the COVID-19 vaccines are composed of positively charged ionizable lipids which undergo an electrostatic interaction with negatively charged mRNA molecules. While LNPs are complex delivery systems, their low toxicity, ability to efficiently encapsulate a variety of genomic payloads (or multiple payloads) and be engineered to specifically target a type of cell present new opportunities for emerging nanomedicines. With growing global interest, demand for LNPs is at an all-time high. The move from a niche application to mainstream has increased investment into bioprocessing development efforts to establish reliable and robust manufacturing with clear scalability and compliance goals in mind.
This article explores the impact of downstream process development on bioactivity and a case study regarding the development of a self-amplifying RNA-LNP COVID-19 vaccine.