Membrane technology for the purification of RNA and DNA therapeutics.

Nucleic acid therapeutics have the potential to revolutionize the biopharmaceutical industry, providing highly effective vaccines and novel treatments for cancers and genetic disorders. The successful commercialization of these therapeutics will require development of manufacturing strategies specifically tailored to the purification of nucleic acids. Membrane technologies already play a critical role in the downstream processing of nucleic acid therapeutics, ranging from clarification to concentration to selective purification. This review provides an overview of how membrane systems are currently used for nucleic acid purification, while highlighting areas of future need and opportunity, including adoption of membranes in continuous bioprocessing.

Pressure-dependent fouling behavior during sterile filtration of mRNA-containing lipid nanoparticles.

The COVID-19 pandemic has generated growing interest in the development of mRNA-based vaccines and therapeutics. However, the size and properties of the lipid nanoparticles (LNPs) used to deliver the nucleic acids can lead to unique phenomena during manufacturing that are not typical of other biologics. The objective of this study was to develop a more fundamental understanding of the factors controlling the performance of sterile filtration of mRNA-LNPs. Experimental filtration studies were performed with a Moderna mRNA-LNP solution using a commercially available dual-layer polyethersulfone sterile filter, the Sartopore 2 XLG. Unexpectedly, increasing the transmembrane pressure (TMP) from 2 to 20 psi provided more than a twofold increase in filter capacity. Also surprisingly, the effective resistance of the fouled filter decreased with increasing TMP, in contrast to the pressure-independent behavior expected for an incompressible media and the increase in resistance typically seen for a compressible fouling deposit. The mRNA-LNPs appear to foul the dual-layer filter by blocking the pores in the downstream sterilizing-grade membrane layer, as demonstrated both by scanning electron microscopy and derivative analysis of filtration data collected for the two layers independently. These results provide important insights into the mechanisms governing the filtration of mRNA-LNP vaccines and therapeutics.