12.2018 | THE SCIENTIST 49NanoTemper Technologies Tycho NT.6
Inscripta MAD7
CRISPR gene-editing technology is a revolu-
tionary tool in the biomedical sciences. But
commercializing products that result from
research that employed CRISPR-Cas9 or
CRISPR-Cpf1 can end up being prohibitively
expensive for many academics and small
startups, as use of the nucleases is associated
with costly licensing fees and royalties.
So, after researchers at Colorado-
based startup Inscripta discovered a new
class of nucleases—named MADzymes as
a nod to the impressive biological diversity
of Madagascar—they made a collective
decision. “We said, this is just too impor-
tant a technology to hold onto,” explains
Inscripta CEO Kevin Ness. “We’re going to
give this enzyme out for free—truly free.”
As of December 2017, the company has
made the entire sequence of its patented DNA-
cutting enzyme, MAD7, available online for all
research and development uses, whether they
are commercial or noncommercial, domestic or
international. Researchers wishing to commer-cialize the enzyme itself—by including the pro-
tein in a therapeutic, for example—are asked to
pay a small royalty.
Louise Baskin, a product manager at
Horizon Discovery, was part of a team that
tested MAD7 and is currently using it to
edit mammalian cells. “All of our data have
pointed to it being as good as Cas9,” she
says. Baskin adds that, because MAD7 has
a different recognition region to Cas9, “it
opens up genomic space in terms of where
we can make those cuts.”
The sequence has been downloaded
more than 1,000 times in the last year,
and Ness says that Inscripta is exploring
options for partnerships with potential dis-
tributors, so that researchers might buy
the DNA or protein product directly.KOEHLER:“Another gene editing product and
an alternative to Cas9. Inscripta aims to break
down barriers related to cost and intellectual
property to enable wider use of gene editing.”The developers of the Tycho NT.6 want to
make quality control of protein samples in
the lab a no-brainer. With older methods,
says NanoTemper Technologies co-CEO
Philipp Baaske, researchers would have
long discussions “about if they should test
the protein or not. Now, they can just do it.”
A run on Tycho takes three minutes and
requires 10 μL of sample. The instrument
heats the sample at a rate of 30 °C/minute
while measuring fluorescence from the
protein’s tryptophan and tyrosine residues,
which it compares to a reference value for
that sample. Discrepancies from that refer-
ence value indicate that the protein may
no longer be folded as it should be, which
would affect its activity, or that the sample
is contaminated or degraded.
Gabriel Birrane, who heads the X-ray
crystallography core at Beth Israel Deacon-
ess Medical Center in Boston, says that hisgroup uses the Tycho in its work with
insoluble bacterial proteins. “We’ve
been able to use the Tycho to screen
conditions” to identify those that will
induce the proteins to fold, he says.
Otherwise, Birrane adds, finding those
conditions can be a difficult trial-and-
error process. And his team has real-
ized that the instrument is faster than
running a gel when they need to verify
that the sample coming off a column
contains their protein of interest.
A desktop Tycho instrument, with
consumables to perform 600 analysis
points, costs $37,500.ZHANG:“Thermal denaturing is a
great tool to quickly assess protein
quality and protein–nucleic acid bind-
ing. Biochemists should find good use
© ISTOCK.COM, NATALI_MIS for this device.”