Frontiers in nonviral delivery of small molecule and genetic drugs, driven by polymer chemistry and machine learning for materials informatics

Abstract

Materials informatics (MI) has immense potential to accelerate the pace of innovation and new product development for polymer-based therapeutic delivery platforms in biotechnology.

Predictive design of multimonomeric polyelectrolytes enables lung-specific gene delivery

“…In this communication, we report the discovery of a three-component polyelectrolyte system that was identified while developing PNP candidates for localization to the lung. Nanite's proprietary platform SAYER™ couples experimental data generation with artificial intelligence (AI) to identify high-performing PNPs for efficient delivery of diverse genetic cargo to tissues outside of the liver 24 (Fig. 1).…”

“…In the current work, aqueous reversible addition–fragmentation chain transfer (RAFT) polymerization 43,44 was employed to prepare a prototypical library via automated liquid handling. 45,46 After screening over 1300 polymers synthesized in house and digitally labelled for training AI models from PNP characterization, in vitro assays, and in vivo biodistribution data, 24 unique monomer candidates emerged for plasmid DNA (pDNA) delivery, based on N -(3-aminopropyl)methacrylamide hydrochloride (APMAm), 2-(trimethylammonio)ethyl methacrylate chloride (TMAEMA), and 3-phenoxy-2-hydroxypropyl methacrylate (PhHPMA). APMAm offers a pH-responsive primary amine that is expected to bind strongly to nucleic acids.…”