Science 360, 436–439 (2018)
Science 360, 439–444 (2018)
Science 360, 444–448 (2018)
Sensitive, specific and portable diagnostics
can rapidly identify viral infections.
Quick and reliable diagnosis of viral disease
in the field can aid treatment and containment.
The recently developed specific high-sensitivity
enzymatic reporter unlocking platform
(SHERLOCK) is based on the programmable
RNA cutting enzyme CRISPR–Cas13 and is
able to identify genetic signatures of viruses
without the need for complex lab protocols.
Gootenberg et al. have developed
SHERLOCK version 2, which offers four
advances: quantitative detection, enhanced
sensitivity, multiplex detection of up to
four viruses (or other nucleic acid targets),
and a visual readout. SHERLOCKv2 can
also detect specific mutations even at very
low frequencies, such as cancer-associated
mutations found in liquid biopsies.
Myhrvold et al. were able to add a step
named HUDSON to the initial SHERLOCK
protocol that allows the detection of
viruses directly from body fluids, creating
a field-deployable diagnostic.
Doudna and colleagues showed that
the enzyme Cas12a has a target-activated
DNA cutting activity that can be leveraged
to detect HPV in patient samples. The
signal-amplifying property of Cas12a
allows rapid and accurate point-of-care
Together these tools will help to bring
portable, accurate diagnostics to the field. HS
NATURE MEDICINE | VOL 24 | JUNE 2018 | 702 | www.nature.com/naturemedicine
© 2018 Nature America Inc., part of Springer Nature. All rights reserved.
Tracing clear cell renal carcinoma evolution
Cell 173, 595–610.e11 (2018) Cell 173, 611–623.e17 (2018)
Cell 173, 581–594.e12 (2018)
Three publications from the TRACERx consortium trace the evolution of clear cell renal
carcinoma (ccRCC), providing insights that can guide therapy in this cancer.
In a whole-genome analysis of 95 biopsies from 33 patients with ccRCC, Swanton,
Campbell and colleagues gain insights into the landmark early genetic mechanisms
in ccRCC development.
With regards to the further evolution of these tumors, Swanton, Larkin and colleagues
analyzed genetic data from 1,206 primary tumor regions from 101 patients with ccRCC. They
find ccRCC evolution and outcome is determined by progressive, identifiable mutations.
Similarly, Swanton and colleagues find in an analysis of 575 primary and 335 metastatic
biopsies across 100 patients with metastatic ccRCC that metastasis is largely driven by
chromosomal aberrations. These create genetic drivers for either rapid progression to
metastasis or attenuated progression, which in turn influences patient mortality. In the
future, genetic evolutionary analysis may aid in standard-of-care decisions. HS
Zika virus shedding in semen
N. Engl. J. Med. 378, 1377–1385 (2018)
Zika virus RNA is commonly shed in the
semen of infected men, and in some of
these men, this occurs beyond 6 months
after the first appearance of symptoms.
Shedding of infectious virus, however,
appears to be limited to the month
immediately after illness onset.
Zika virus is transmitted by mosquitoes
and during recent outbreaks has been
linked to the development of congenital
microcephaly in the offspring of infected
individuals. There have been reported cases
of male-to-partner sexual transmission,
but the duration of contagion is unknown.
Mead et al. analyzed levels of Zika
virus RNA in semen samples from 184
symptomatic men (1,327 total samples)
every 2 weeks over a period of 6 months.
Zika virus RNA was commonly detected,
and the duration of shedding was linked
to ejaculatory frequency and joint pain.
Detection of infectious virus in semen
was less common and was rarely observed
beyond the first few weeks of illness onset.
Interruption of sexual activity during the
early symptomatic phase of Zika in men could
be important in preventing transmission. HS
brain-resident innate immune cells called
microglia and results in altered later
development of neuropathologies in mice.
Previous exposure of myeloid cells to
immune stimuli can result in immune training,
in which subsequent immune responses are
exacerbated, or immune tolerance, in which
later immune responses are inhibited.
Wendeln et al. found that exposing a
mouse engineered to develop Alzheimer’s
disease pathology to a peripheral immune
stimulus that results in immune training
increased Alzheimer’s neuropathology, and
exposing this mouse to a peripheral immune
stimulus that induced tolerance decreased
Alzheimer’s neuropathology. These effects
were mediated through epigenetic changes
in the microglia. They also found that
previous immune exposure modulated
In humans, it is possible that previous
exposure to infection or other inflammatory
conditions in the periphery might
mimic these immune memory effects on
neurological disease. HS
Nature 556, 332–338 (2018)
The memory of previous immune stimuli
peripheral to the brain is mediated by
RECOMBINANT PROTEIN THERAPY
In utero correction of a
N. Engl. J. Med. 378, 1604–1610 (2018)
The genetic disorder X-linked hypohidrotic
ectodermal dysplasia (XLHED) results in a
lack of the protein ectodysplasin A in affected
individuals, preventing the development
of sweat glands, and can be corrected by
amniotic delivery of the missing protein.
Individuals affected by XLHED can
develop life-threatening hyperthermia
after birth due to their inability to sweat.
Researchers from the University of Erlangen
injected the receptor-binding domain of EDA
intraamniotically into two pregnant women,
one with a single fetus and one with twins.
These fetuses were known to be affected
by XLHED from noninvasive screening
and because they have affected siblings.
Once born, the three infants were able to
sweat normally. Importantly, the authors’
mechanistic studies in mice show that the
protein had to be taken up systemically by
the developing offspring to be effective.
Although long-term follow-up has yet to be
carried out, this study shows the effectiveness of
prenatal protein therapy for this genetic disease
at critical time periods in development. HS