The past two decades have seen growing interest in the development of nucleic acid-based therapies for the treatment of a wide range of genetic disorders as well as for use as novel vaccines. This includes the use of DNA to replace malfunctioning genes, e.g., in the treatment of hemophilia, as well as the use of short interfering and micro RNA (siRNA and miRNA) for gene silencing or post-transcriptional regulation of gene expression. There are currently more than 200 ongoing clinical studies of RNA-based therapeutics listed on www.clinicaltrials.gov, with even greater numbers of trials of DNA-based therapeutics.

Most work on nucleic acid purification has focused on laboratory-scale methods, many of which would be very difficult to employ for commercial manufacturing.  The objective of this project is to develop cost-effective membrane processes suitable for the large-scale purification of DNA and RNA-based therapeutics.

 

Manzano, I., and A. L. Zydney “Quantitative study of RNA transmission through ultrafiltration membranes,” J. Membrane Sci., 544, 272-277 (2017).

Li, Y., K. Zhu, A.L. Zydney, “Effect of ionic strength on membrane fouling during ultrafiltration of plasmid DNA,” Sep. Purif. Tech., 176: 287-293 (2017).

Li, Y., N. Butler, A.L. Zydney, “Size-based separation of supercoiled plasmid DNA using ultrafiltration,” J. Colloid Interf. Sci., 472: 195-201 (2016).

Li, Y., D. Currie, A.L. Zydney, “Enhanced purification of plasmid DNA isoforms by exploiting ionic strength effects during ultrafiltration,” Biotech. Bioeng., 113: 783-789 (2016).

Li, Y., E. E. Borujeni, and A. L. Zydney “Use of preconditioning to control membrane fouling and enhance performance during ultrafiltration of plasmid DNA,” J. Membrane Sci., 479, 117-122 (2015).