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Manufacture Small Molecules, Technology and Equipment

Protein Synthesis – But Not as We Know It

In a previous issue of The Medicine Maker, we reported on the work of James Collins, a faculty member at the Wyss Institute at Harvard University and the Henri Termeer professor of medical engineering and science at MIT (1). Collins and his colleagues are not working with DARPA or focusing on synthesizing drugs on demand, but they have developed a method for producing therapeutic molecules on-demand with freeze-dried synthetic gene networks (2). The technique could be used to produce complex biopharmaceuticals that do not require refrigeration – making them ideal for use in the developing world. “The lyophilized format negates the need for a cold chain, and is very simple to use – it requires only the addition of water to synthesize the protein of interest,” explains Collins.

The work of the Collins Lab focuses on engineered gene networks using synthetic biology and systems. “Our work brings together engineers and molecular biologists to model, design and construct synthetic gene circuits, and to use these to reprogram living organisms for specific applications,” he says. “The work stems from the Human Genome Project in the 1990s – the project produced large ‘parts lists’ for different organisms. We want to explore engineering these ‘parts’ into new and useful combinations.”

To create the freeze-dried synthetic gene networks, a mixture of DNA, RNA, ribosomes and enzymes is removed from the cell and adsorbed to a solid support, such as paper. The preparation is freeze-dried and stored at room temperature – and protein synthesis takes place as normal once water is added.

“We have shown that these preparations can be the basis for rapid and inexpensive point-of-care diagnostics such as for Ebola and Zika (3). Now, we are investigating the use of similar cell-free extracts, but non-adsorbed, to make therapeutic proteins on demand (4),” says Collins. “These could be beneficial for providing biotherapeutics in remote locations, such as in emergency relief efforts, or in space.”

Looking ahead, Collins and his colleagues are investigating the advantages of embedding the dried systems into clothing, for example, to serve as sensors to warn of exposure to an infectious agent, or as components of educational kits for students.

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<link issues protein-synthesis-but-not-as-we-know-it>Protein Synthesis – But Not as We Know It

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  1. J Strachan, “Freeze-Dried Pharma”, The Medicine Maker, 23 (2017).
  2. K Pardee et al. “Paper-Based Synthetic Gene Networks”, Cell, 4, 940-954 (2014).
  3. K Pardee et al. “Rapid, low-cost detection of Zika virus using programmable biomolecular components”, Cell, 165, 1255-1266 (2016).
  4. K Pardee et al. “Portable, on-demand biomolecular manufacturing”, Cell, 167, 248-259 (2016).
About the Author
James Collins

James Collins is a faculty member at the Wyss Institute at Harvard University and the Henri Termeer professor of medical engineering and science at MIT.

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