From Bench to Bedside: The Unsolved Scale-Up Bottlenecks in Lipid Nanoparticle Manufacturing for Personalized RNA Therapeutics

Abstract

The advent of RNA‑based therapeutics encompassing messenger RNA (mRNA), self‑amplifying RNA (saRNA), and CRISPR ribonucleoprotein (RNP) systems—has ushered in a transformative era of precision medicine. Whereas this the transition from laboratory‑scale precision to full‑scale industrial production presents a fundamental engineering tradeoff. This paper examines how design choices, equipment capabilities focus on biopharmaceutical manufacturing, advanced materials, and Micronanolipidformulation. The bottle necks we add in our review are the formation of nano bio interference, IVIVC failuer, the scalability of process and how the continuous manufacturing is processed Moreover, the rise of personalized medicine introduces N = 1 production scenarios, demanding decentralized Good Manufacturing Practice (GMP) frameworks and sophisticated cold‑chain logistics to ensure stability and timely patient access. we are proposing the future plan and road map in the precised  RNA therapeutic forming the next generation aisa designed lipid libraries, on Demand self amplifiig RNA factories and regulated autonomous LNP Micro factories.