Quantitative study of RNA transmission through ultrafiltration membranes

Nucleic acid-based therapies have the potential to treat a wide range of diseases through their ability to silence and/or regulate gene expression. Strategies for the large-scale purification of RNA are still being developed, creating a need for more fundamental understanding of the behavior of RNA in different separation systems. The objective of this work was to evaluate RNA transmission through a series of composite regenerated cellulose and polyethersulfone ultrafiltration membranes with different molecular weight cutoffs. Data were obtained using Torula yeast RNA, with the size distribution evaluated by both dynamic light scattering and agarose gel electrophoresis. Results with dilute RNA solutions were strongly influenced by RNA adsorption to the composite regenerated cellulose membrane; this effect was not seen with the polyethersulfone membranes. Data for the polyethersulfone membranes were analyzed using the concentration polarization model, which describes the affects of bulk mass transfer on RNA transmission, in combination with available hydrodynamic models for membrane transport. The results provide important insights into the factors controlling RNA transmission and the potential for using ultrafiltration for the purification of nucleic acid therapeutics.