Multimodal chromatography for the selective capture of pre-miRNA-29b therapeutics

Nucleic acid-based treatments have become increasingly important in addressing diseases linked to genetic defects. In Alzheimer's disease, decreased levels of microRNA-29b lead to the overproduction of the human beta-secretase 1 (hBACE1) enzyme, which is associated with the progression of the condition. Consequently, pre-miR-29b represents a promising therapeutic agent, as restoring its levels could diminish hBACE1 expression and reduce amyloid-beta accumulation in neuronal cells. However, the successful deployment of pre-miRNA-29b as a treatment relies heavily on ensuring its purity, stability, and biological potency. This work evaluates the selective purification of pre-miRNA-29b, recombinantly produced from Rhodovulum sulfidophilum, using Capto Q ImpRes, a multi-modal strong anion exchange resin. The research optimizes process parameters, such as NaCl concentration and pH, to maximize the recovery and purity of pre-miRNA-29b through a Central Composite Design (CCD). The results reveal a relationship between recovery and purity, with CCD predicting optimal conditions yielding up to 48.21% recovery and 51.15% purity of pre-miRNA-29b. Overall, this work highlights the potential of using multimodal resins to selectively capture pre-miRNA-29b from complex recombinant samples. This selectivity demonstrates the promise of this technique for the isolation of specific RNA molecules, a crucial step in the development of effective nucleic acid-based therapies. These findings contribute to the ongoing efforts to establish highly effective purification strategies that ensure the quality of therapeutic RNAs.