Scalable multimodal weak anion exchange chromatographic purification for stable mRNA drug substance

Author:

Megušar Polona1,Miklavčič Rok1,Korenč Matevž1,Ličen Jure1,Vodopivec Tina1,Černigoj Urh1ORCID,Štrancar Aleš1,Sekirnik Rok1ORCID

Affiliation:

1. Sartorius BIA Separations d.o.o. Ajdovščina Slovenia

Abstract

AbstractMessenger RNA (mRNA) has emerged as a modality with immense therapeutic potential. Recent innovations in production process of mRNA call for procedures to isolate pure mRNA drug substance (DS) with high yield, high capacity, scalability, and compatibility with GMP production systems. Novel RNA modalities, such as circular RNA (circRNA), have further driven the need for non‐affinity capture possibilities which are already widely used in the biopharmaceutical industry, for example, in monoclonal antibody processing. The principle that multimodal ion exchange/hydrogen bonding chromatography can be used to separate mRNA from in vitro transcription components has recently been demonstrated. Here, we apply and refine this approach to be suitable for scalable purification of multiple mRNA constructs with sufficient yields, purity, and stability, for use in mRNA production process. Binding capacity of the PrimaS‐modified monolithic chromatographic column for mRNA enabled up to 7 mg/mL product isolation in a single chromatographic run, with 98% recovery and room temperature stability of the eGFP mRNA demonstrated for up to 28 days. This approach is independent of construct size or the presence of polyadenylic acid tail and is applicable for capture of a wide variety of RNAs, including mRNA, self‐amplifying RNA, circRNA, and with optimization also smaller RNAs such as transfer RNA and others.

Publisher

Wiley

Subject

Clinical Biochemistry,Biochemistry,Analytical Chemistry

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Editorial;ELECTROPHORESIS;2023-12

2. High Recovery Chromatographic Purification of mRNA at Room Temperature and Neutral pH;International Journal of Molecular Sciences;2023-09-19

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