Work

Model-Based Analysis of Membrane-Enhanced Liquid-Phase Oligonucleotide Synthesis

Year: 2025

Type: article

Abstract: Oligonucleotides show great promise for therapeutic applications. While traditional solid-phase oligonucleotide synthesis presents manufacturing challenges due to low scalability, lack of real-time monitoring and high process mass-intensity, liquid-phase synthesis (LPOS) combined with soluble anchors and membrane diafiltration has emerged as a viable alternative. Herein, we formulate a multi-stage dynamic model of the LPOS process using a multi-branched homostar support hub. We exploit this model to analyse the interplay between the durations of the reaction and diafiltration steps on the oligonucleotide yield and purity through the solution of an inverse feasibility problem.

Source: IFAC-PapersOnLine

DOI: 10.1016/j.ifacol.2025.07.158

Authors: Alberto Saccardo, Benoît Chachuat

Institution: Imperial College London

Language: English

Topic: Process Optimization and Integration

Subfield: Control and Systems Engineering

Field: Engineering

Domain: Physical Sciences

Open Access status: diamond

Funder: Innovate UK

Award: Sustainable bioprocess for oligonucleotide manufacture using Nanostar Sieving (BioNanostar)