Biologics on-demand: DARPA and MIT look to manufacture on the battlefield

By Melissa Fassbender

- Last updated on GMT

Image: iStock/kanyakits
Image: iStock/kanyakits

Related tags Gene expression

The US Department of Defense has developed a portable, on-demand biopharmaceutical production system that could be used in warzones to make treatments at point-of-care.

The platform was developed as part of a US Defense Advanced Research Projects Agency (DARPA) program to provide far-forward-deployed Service members “what they need when they need it, obviating the need for individual drug stockpiling, cold storage, and complex logistics,”​ Tyler McQuade, program manager for DARPA's Battlefield Medicine program, told

The platform, developed in conjunction with researchers at the Massachusetts Institute of Technology (MIT), consists of a biologics expression system engineered to secrete multiple therapeutic proteins and a millilitre-scale perfusion microfluidic platform.

DARPA has also funded a similar project​ with the University of Maryland, Baltimore County – sponsored by Thermo Fisher, Ohio State and Latham Biopharm - aimed at making life-saving biologics in under eight hours using a portable briefcase-sized kit for use in a warzone but with applications for public quarantines, personalised medicine, and ultra-low cost vaccine manufacturing.

Tactical Challenges

According to McQuade, the development team had to overcome the challenge of integrating end-to-end manufacturing processes from synthesis to purification to formulation which are traditionally decoupled and performed in different locations.

Rajeev Ram, a professor of electrical engineering at MIT, added that achieving sufficient control to turn off the expression of one protein while turning on the expression of another - needed to ensure minimal cross-contamination between various drugs - had also posed a challenge.

However, “the most significant challenge was producing a sufficient quantity of material from a portable system within 24 hours​,” he told us.

Battling the problems

Addressing these challenges required both novel genetic engineering, known as synthetic biology, and control of the chemical environment of the cells using microfluidics.

“While the yeast strain used here - Pichia pastoris - has been used in biomanufacturing commercially, many of the tools for genetic engineering and control were demonstrated for the first time in this paper,”​ said Ram.

“These synthetic gene circuits allow the control of expression with a variety of chemical triggers,”​ he explained. “The next step was to rapidly change the chemical trigger without losing the cells.”

Ram explained that the microbioreactor uses a membrane filter to retain the cells as the fluid is quickly flushed out. This rapid perfusion of fluid through the membrane allowed the researchers to reset the chemical environment while holding the cells in the microbioreactor.

“In this way, we were able to switch the protein being expressed and secreted within two hours.”

Source: Nature Communications

Title: Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care

Authors: Pablo Perez-Pinera et al.


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