Publications
medRxivOct 2025 DOI:
10.1101/2025.10.15.25338083

Automated Cell-free Protein Synthesis for Distributed Biomanufacturing

Silva, Severino Jefferson Ribeiro da; Simchi, Mohammad; Matthews, Quinn; Bayat, Pouriya; Vigar, Justin R. J.; Singh, Serena; Iwe, Idorenyin A.; Santos, Bárbara Nazly Rodrigues; Duplat, David; Bolívar, Paulina; Bozovičar, Krištof; Fobel, Ryan; Tinafar, Aidan; Cicek, Seray; Guo, Yuxiu; Masum, Fahim; Cranmer, Lauren A.; Norouzi, Masoud; Mendes, Renata Pessôa Germano; Leon, Cielo; Machado, Laís Ceschini; Wu, Wentao; Talebi, Soheil; Klenov, Alexander; Rayhan, Ashyad; Magalhães, Jurandy Júnior Ferraz de; Narváez, Carlos F.; Charania, Moiz A.; Paiva, Marcelo Henrique Santos; Wallau, Gabriel Luz; Mazzulli, Tony; Sinton, David; Bernal, Adriana; González, Camila; Pena, Lindomar; Pardee, Keith
Product Used
Genes
Abstract
ABSTRACT Recombinant proteins are fundamental to modern medicine, enabling research, diagnostics, and drug discovery, yet their access is often restricted by centralized manufacturing and cold-chain distribution. Decentralized, on-site biomanufacturing can enable research, provide resilience, and advance personalized medicine. Here, we introduce MANGO (MANufacturing on the GO), a purpose-built, open-source device designed for automated, benchtop cell-free protein synthesis and purification. Computer-controlled synthesis and purification are mediated through biomedical-grade pumps, valves, and a microchannel manifold, enabling rapid protein production directly at the point-of-use. To demonstrate MANGO’s utility, we produced and validated a diverse range of proteins, including nanobodies against SARS-CoV-2 and TNF, cloning enzymes, and diagnostic enzymes, with performance equivalent to their commercial counterparts. We further deployed MANGO in Brazil and Colombia to support patient trials for SARS-CoV-2 and dengue virus diagnostics. These results establish MANGO as a low-cost, portable platform that can democratize access to bioreagents in both high- and low-resource settings and, ultimately, expand participation in the bioeconomy.
Product Used
Genes

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