background image
cellular extracts are simply freeze-dried into
pellets, which remain stable for at least a
year. To activate protein production, the
researchers add water to rehydrate the
pellets, along with freeze-dried DNA that
encodes the desired protein.
This approach could be useful for generat-
ing a wide range of products, including both
drugs and molecules that could be used
to diagnose illness. In the Cell study, the
researchers produced small proteins that
could be used as a diphtheria vaccine, as
well as antimicrobial peptides, which hold
potential to fight bacterial infections.
They also programmed the pellets to gener-
ate enzymes that form a multistep metabol-
ic pathway that synthesizes a complex drug
known as violacein, which has anticancer
and antibiotic activity.
For diagnostic applications, the researchers
used the pellets to produce several different
types of antibodies, including one that can
detect the bacterium Clostridium difficile,
which can produce severe inflammation of
the colon.
Easy storage
This approach could prove easier than using live cells to generate biophar-
maceuticals because the freeze-dried components are easy to store and
ship, and they don¡¯t need to be refrigerated.
¡°Collins and colleagues paint a future where freeze-dried, cell-free biomanu-
facturing platforms can be used to synthesize therapeutics, vaccines, and
biochemicals on demand, without the need for a cold [supply] chain,¡± says
Michael Jewett, an associate professor of chemical and biological engineering
at Northwestern University, who was not involved in the research. ¡°By mov-
ing manufacturing from the factory to the front lines, we might be able to
provide patient-specific medicines where medicines are not available now.¡±
Collins anticipates that this type of technology should be useful in a variety
of settings.
¡°It could be used in a very simple carry kit for health care workers going in
the field in developing regions,¡± he says. ¡°We think it could be very useful
for the military, when you¡¯re going out on a mission in the field, or for hikers
and athletes going for long hauls. You could even have it in the back of your
car as an expanded first aid kit.¡±
(continued on page 3 >>)
Moving Medicine Manufacturing From Factory to Front Lines
To produce biopharmaceuticals on demand, just add water
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Freeze-dried cellular components can be
rehydrated to churn out useful proteins
Anne Trafton, MIT News Office, September
22, 2016: Researchers at MIT and other insti-
tutions have created tiny freeze-dried pellets
that include all of the molecular machinery
needed to translate DNA into proteins, which
could form the basis for on-demand produc-
tion of drugs and vaccines.
The pellets, which contain dozens of enzymes
and other molecules extracted from cells, can
be stored for an extended period of time at
room temperature. Upon the addition of water
and freeze-dried DNA, the pellets begin pro-
ducing proteins encoded by the DNA.
¡°It¡¯s a modular system that can be pro-
grammed to make what you need, on the
spot,¡± says James Collins, the Termeer Profes-
sor of Medical Engineering and Science in
MIT¡¯s Department of Biological Engineering
and Institute for Medical Engineering and
Science (IMES). ¡°You could have hundreds of
different DNA pellets you can add in the field.¡±
These pellets, a few millimeters in diameter,
2016 OCT/NOV #7-5
could be easily carried by soldiers, astronauts, or health care workers
heading to remote areas, says Collins, who is the senior author of a paper
describing this strategy in the Sept. 22 online edition of Cell.
The paper¡¯s lead authors are Keith Pardee, an assistant professor at the
University of Toronto and former research scientist at Harvard University¡¯s
Wyss Institute for Biologically Inspired Engineering; Shimyn Slomovic, an
IMES postdoc; Jeong Wook Lee, a Wyss Institute research scientist; and
Peter Nguyen, a Wyss Institute Technology Fellow.
Cell-free synthesis
Collins and many others in the growing field of synthetic biology have
previously designed cells to perform many functions they don¡¯t normally
have, such as producing drugs or biofuels. Over the past few years, Col-
lins has shown that this kind of design can also be done outside of cells,
by extracting the necessary cellular components and freeze-drying them
onto paper or other materials.
¡°The cell-free extracts consist of a few dozen enzymes, DNA, and RNA, as
well as ribosomes and other molecular machines leading to transcription
and translation,¡± Collins says.
In the new study, the researchers took the paper out of the equation: The
Researchers at MIT and other institutions have created tiny
freeze-dried pellets that include all of the molecular machinery
needed to translate DNA into proteins, which could form the
basis for on-demand production of drugs and vaccines. Image:
Christine Daniloff/MIT. Antimicrobial peptide illustration by
Ymahn/Wikimedia Commons.