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Principal Investigator: Jinxiang Zhou
Organization: PURILOGICS, LLC
Fiscal Year: 2020
Award: $289,381
Funding agency: National Institute of General Medical Sciences
Project Summary
This SBIR Urgent Competitive Revision will develop the first affinity membrane to purify therapeutic mRNA with
high selectivity and throughput. mRNA-based pharmaceuticals have potential to address a wide variety of
pathologies. mRNA-based vaccines can increase safety and dramatically shorten development timelines in
pandemic scenarios. A number of mRNA-based COVID-19 vaccines are under development, and one such
vaccine has completed its Phase-I clinical trial and showed great promise as a response to the COVID-19
pandemic. However, a company pioneering mRNA medicines has revealed that the lack of high throughput
downstream purification processes is a major hurdle that must be addressed in the upscaling of industrial
mRNA production to yield the necessary quantity and quality. Considering the profound impact that COVID-19
will have on the global population of nearly seven billion people, the time to develop a high productivity mRNA
purification technology, like the one proposed, is now. By addressing this challenge, the proposed technology
will have a significant impact on mRNA production and, by association, improve patient accessibility to the
vaccine. Therapeutic mRNA usually possesses a polyadenylic acid (poly-A) tail. Oligo-deoxythymidine (oligo-
dT) has been recognized as effective affinity ligand to isolate polyadenylated mRNA from feed streams via
hybridization between adenine in the poly-A tail and deoxythymidine in oligo-dT. The goal of this Competitive
Revision project is to demonstrate the feasibility of developing dT-based affinity membrane products with high
binding capacity for the rapid and selective purification of polyadenylated mRNA. Preliminary data are highly
encouraging. The products derived from this innovation will be first-in-market, disposable membrane
chromatography columns that can improve the mRNA purification productivity up to one hundred times with
high purity and yield compared to conventional resin columns. The Specific Aims of the study are to (1)
synthesize and characterize mRNA affinity membranes and (2) test prototype affinity membrane columns for
capture step purification of polyadenylated mRNA. In Specific Aim 1, Purilogics will evaluate the roles played
by ligand structure and density, synthesis conditions, and bind-and-elute conditions on capacity and recovery
using a commercially available purified mRNA. In Specific Aim 2, Purilogics will collaborate with a partner
contract manufacturing organization to quantify membrane column performance for capture step purification of
polyadenylated mRNA prepared with in vitro transcription (IVT) processes. The prototypes also will be
benchmarked against existing products. Multiple iterations of synthesis and performance characterization will
improve membrane performance. Immediate market entry for the new column products will be sales to
purification scientists and engineers in biopharmaceutical companies.
Terms: <1H-Purin-6-amine><2'-Deoxythymidine><Abscission><Acids><Address><Adenine><Affinity><Benchmarking><Best Practice Analysis><Binding><Biologic Products><Biologic Sciences><Biological><Biological Agent><Biological Products><Biological Sciences><Bioscience><Buffers><Businesses><COVID-19><COVID-19 epidemic><COVID-19 pandemic><COVID-19 vaccine><COVID19><COVID19 epidemic><COVID19 pandemic><COVID19 vaccine><Chromatography><Column Chromatography><Consumption><Contracting Opportunities><Contracts><Coronaviridae><Coronavirus><DThyd><Data><Deoxythymidine><Development><Early-Stage Clinical Trials><Engineering><Enzyme Gene><Enzymes><Excision><Extirpation><Gene Transcription><General Population><General Public><Genetic Transcription><Goals><Health><Human><In Vitro><Industrialization><Industry><Legal><Length><Life Sciences><Ligands><Manufacturer><Manufacturer Name><Mass Vaccinations><Medicine><Membrane><Messenger RNA><Modern Man><Molecular Interaction><Oligo><Oligonucleotides><Organic Chemistry><Pathology><Patients><Performance><Pharmaceutical Agent><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phase><Phase 1 Clinical Trials><Phase I Clinical Trials><Plant Resins><Play><Poly(A) Tail><Poly(A)+ mRNA><Polyadenylated mRNA><Polymer Chemistry><Population><Process><Production><Productivity><Proteins><RNA Expression><Recovery><Removal><Role><SBIR><Safety><Sales><Scientist><Small Business Innovation Research><Small Business Innovation Research Grant><Speed><Standardization><Stream><Structure><Surgical Removal><TdR><Technology><Testing><Therapeutic><Thymidine Deoxyriboside><Time><TimeLine><Transcription><Transcription Process><Vaccine Clinical Trial><Vaccine Production><Vaccines><Validation><Vitamin B4><base><biopharmaceutical><biotherapeutic agent><corona virus><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><coronavirus disease 2019><coronavirus disease 2019 epidemic><coronavirus disease 2019 pandemic><coronavirus disease 2019 vaccine><cost effective><density><developmental><improved><innovate><innovation><innovative><mRNA><membrane structure><membrane synthesis><novel><oligo (dT)><oligodeoxythymidylic acid><oligos><pandemic><pandemic disease><phase I protocol><plasmid DNA><polyadenylated messenger RNA><processing speed><protein purification><prototype><public health relevance><resection><residence><residential building><residential site><resin><response><social role><tool><vaccine safety>