Abstract: The present invention relates, in part, to methods, systems and processes for large-scale purification of mRNA using a filtering centrifuge operating at lower gravitational forces. The invention also relates to compositions of purified mRNA and uses thereof.

Abstract: The present invention provides, among other things, methods for purifying high quality messenger RNA (mRNA) suitable for clinical use, without using any caustic or flammable solvents. The present invention is, in part, based on surprising discovery that mRNA can be successfully purified by selective precipitation and washing without using ethanol while maintaining integrity and high purity of mRNA. Thus, the present invention provides an effective, reliable, and safer method of purifying RNA from large scale manufacturing process therapeutic applications without using any caustic or inflammable solvents.

Abstract: The present invention provides, among other things, methods for purifying high quality messenger RNA (mRNA) suitable for clinical use, without using any caustic or flammable solvents. The present invention is, in part, based on surprising discovery that mRNA can be successfully purified by selective precipitation and washing without using ethanol while maintaining integrity and high purity of mRNA. Thus, the present invention provides an effective, reliable, and safer method of purifying RNA from large scale manufacturing process therapeutic applications without using any caustic or inflammable solvents.

Abstract: The present invention provides, among other things, methods for large-scale production of a composition comprising full-length messenger RNA product that is substantially free of double-stranded RNA, and compositions produced using such methods and uses thereof. The present invention is based, in part, on the surprising discovery that mRNA product produced by in vitro transcription using an SP6 RNA polymerase is substantially free of double-stranded RNA. In one aspect, the present invention provides methods of generating large-scale mRNA product for mRNA therapy without need for a chromatography step.

Abstract: The present invention provides, among other things, methods for purifying mRNA, which involves removing impurities from a messenger RNA preparation synthesized by large scale in vitro transcription process (IVT), by precipitating the IVT-synthesized mRNA in a buffer comprising a denaturing salt in combination with a reducing agent, followed by capturing the precipitated mRNA and dissolving the captured mRNA into a solution to obtain purified mRNA.