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Sustainable bioprocess for oligonucleotide manufacture using Nanostar Sieving (BioNanostar)

Lead Participant: EXACTMER LIMITED

Abstract

The oligonucleotide synthesis landscape is undergoing a transformative shift, and Exactmer, in collaboration with the University of Manchester and Imperial College, is at the forefront with the Sustainable bioprocess for oligonucleotide manufacture using NanostarSieving (BioNanostar) project. Oligonucleotide-based therapeutics, face hurdles in manufacturing that hinder broad adoption. The prevailing Solid Phase Synthesis (SPS) method, known for high Process Mass Intensity (PMI) and cost inefficiencies, is a limiting factor in large-scale production.

Nanostar Sieving, Exactmer's proprietary platform, revolutionizes oligonucleotide synthesis through a liquid-phase approach. The iterative addition of nucleotide monomers to a growing Nanostar hub, coupled with membrane filtration, yields precise oligo sequences with scalability, reduced errors, and real-time monitoring.

Exactmer's Nanostar Sieving technology offers promise in scalable oligo synthesis. This chemistry-agnostic, liquid-phase platform uses membrane filtration to address SPS limitations, providing scalability, cost reduction, and environmental sustainability. Challenges persist in handling organic solvents, sensitive reagents, and low reagent solubility.

BioNanostar aims to pioneer a sustainable, efficient, and cost-effective oligo assembly method, integrating Nanostar Sieving with enzyme technology for linear oligo assembly in aqueous media. Digital modeling techniques, aided by model-based design of experiments (MBDoE), will optimize parameters, using enzymes for specificity and efficiency, and membrane filtration for purification at each step.

BioNanostar combines Nanostar Sieving with linear enzymatic assembly, optimizing parameters through deploying digital solutions. Objectives include Exactmer Chemical Process optimization, bio-synthesizer design, and advanced membranes for aqueous media. The telescoping of Nanostar Sieving with enzymatic assembly promises enhanced oligo manufacturing, utilizing aqueous media for a greener process. The shift to nucleoside triphosphate (NTPs) as building blocks is a crucial advancement.

This 24-month collaborative effort envisions a streamlined bioprocess for linear oligo assembly. The Exactmer--University of Manchester--Imperial College consortium uniquely positions itself to pioneer a more sustainable, efficient manufacturing process, reducing final product costs and introducing a novel, adaptable method for oligonucleotide synthesis, impacting a range of diseases.

In conclusion, BioNanostar is a pioneering initiative set to impact oligo bio-manufacturing. The integration of cutting-edge technologies, sustainability, and efficiency aligns with this competition goals, promising advancements in bioprocessing and biomanufacturing of oligos. BioNanostar has the potential to revolutionize the oligonucleotide synthesis landscape, making it more sustainable, cost-effective, and accessible for therapeutic applications.

Lead Participant

Project Cost

Grant Offer

EXACTMER LIMITED £814,607 £ 570,225
 

Participant

THE UNIVERSITY OF MANCHESTER £149,802 £ 149,802
IMPERIAL COLLEGE LONDON £514,590 £ 514,590

Publications

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