Fast, On-Demand Manufacturing of Room Temperature-Stable RNA

A method enabling facile synthesis and purification of RNA in a stable format that does not require cold chain distribution.
Problem:
The cold storage conditions required in the distribution of RNA-based therapies presents a major roadblock toward expanding the utility of these medicines. RNA is susceptible to degradation in aqueous environment and thus necessitates cryogenic (the production of materials at very low temperatures) transport and storage. The mRNA-based COVID-19 vaccines from Pfizer and Moderna, for instance, require storage at -70 °C and -20 °C, respectively. This amounts to a huge cost for maintaining the ultracold chain system. Therefore, a method enabling streamlined RNA synthesis and separation of products into a stable environment would mitigate such costs and widen the accessibility of the growing class of RNA-based treatments.
Solution:
Daeyeon Lee and his team developed a method for simultaneous RNA production and separation. The more efficient and simplified workflow makes local, on-site manufacturing feasible, removing the need for costly product distribution. The approach also yields an RNA product that partitions into an oil phase where it is less prone to degradation, further lessening the need for cryogenic storage.
Technology:
The RNA-manufacturing platform is a two-phase system made up of an aqueous phase and an oil/organic phase. The aqueous phase contains DNA serving as a template to transcribe into RNA via enzymatic catalysis at the oil-aqueous interface. Selective binding of lipids to RNA leads to separation of the RNA product into the oil phase, where it can remain stored at room temperature. Central to this system is a complex form of liquid mixture known as bicontinuous interfacially jammed emulsion gel (bijel). The highly interwoven structure of the dual-phase bijel allows reactants to efficiently feed into the aqueous phase while the products get extracted from the oil phase. This enables continuous rapid reaction and separation of products.
Advantages:

Bijel provides two orders of magnitude larger oil-water interfacial area compared to conventional membranes
Large interfacial area facilitates high reaction rates at room temperature and rapid separation of products in a small volume reactor
Permits on-site, on-demand RNA production and improves manufacturing resiliency
Faster and less expensive RNA production
Does not require cryogenic storage of RNA product
RNA product is stable at room temperature, in contrast to -70 °C or -20 °C for the mRNA-based COVID-19 vaccines from Pfizer and Moderna, respectively
Potential translation of platform to other types of pharmaceuticals, such as small molecule chiral drugs

Stage of Development:

Concept

(a) Schematic of the biphasic system used for continuous RNA production and separation. (b) Schematic of a close-up view of bijel, wherein the reactants (DNA nucleotides) feed into the water phase while the product exits into the oil phase. (c) The highly intertwined water and oil phases in the bijel are separated by a layer of nanoparticles equipped with RNA polymerase to enable enzyme-catalyzed conversion of DNA into RNA.
Intellectual Property: