09/17/2024
By Danielle Fretwell

The Francis College of Engineering, Department of Chemical Engineering, invites you to attend a Doctoral Dissertation defense by Richard Marx on: Rethinking Classical Cellulose Oligo(dT) mRNA Purification for Next-Generation mRNA Therapeutics

Candidate Name: Richard Marx
Degree: Doctoral
Defense Date: Tuesday, Sept. 24, 2024
Time: 10 a.m. EST
Location: Please contact the advisor or student for location.

Committee:

  • Advisor: Seongkyu Yoon Chemical Engineering Professor UMass Lowell
  • Dongming Xie, Ph.D., Associate Professor, Chemical Engineering, UMass Lowell
  • Malcolm Pluskal, Ph.D., Chief Science Officer, Landrau Scientific Innovations
  • Jasdave Chahal, Ph.D., Chief Scientist, Tiba Biotech
  • Juan Manuel Artes Vivancos, Ph.D., Associate Professor, Chemistry, UMass Lowell
  • Soumita Das, Ph.D., Associate Professor, Biomedical & Nutritional Science, UMass Lowell

Brief Abstract:
The efficacy and safety of messenger ribonucleic acid (mRNA)-based vaccines and therapeutics require highly purified mRNA free of known in vitro transcription reaction byproducts such as RNA fragments and double-stranded RNA. This purification has been safely and effectively demonstrated by immobilizing oligo-deoxythymidilic acid (Oligo dT) to an affinity chromatography support. Commonly used Oligo dT mRNA resins were developed for smaller (covid-like) mRNAs and are challenged to separate large mRNAs (>8,000 nt) efficiently. Here, we investigate functionalizing Oligo dT on a cellulose monolith-like particle specifically developed for large-target (5-300 nm) industrial chromatographic applications. The Oligo dT MLP was optimized for mRNA affinity chromatography separations by 40 base pair Oligo Poly Adenosine dynamic binding capacity and then tested with three separate mRNA sizes (977, 2480, and 8803 nt). The results revealed that the open pore size of the monolith provided additional surface area accessible to all the mRNAs, providing consistent dynamic binding capacity across all three mRNAs. Large mRNAs often cause a steep decline in resin DBC, as seen here, resulting in the MLP displaying up to 448% higher DBC with more consistent elution behavior and improved recovery. This investigation supports mRNA research, targeting larger and more complex proteins, improving manufacturing efficiency and enabling more cost-effective therapies.