- New tool enables the CRISPR-based diagnostic SHERLOCK
to detect viruses directly from body fluids.
- The expansion of the
platform's potential allows to quickly and cheaply track pathogens such as
Zika and Ebola during an outbreak.
- The tool eliminates a processing step that
previously required a lab environment and professionally trained
CRISPR-based diagnostic SHERLOCK has been
optimized for rapid use during viral outbreaks by research teams at Broad
Institute of MIT and Harvard. The new tool updates SHERLOCK which was first
unveiled in 2017, to detect pathogens quickly and cheaply directly from body
fluids. The study is published in the journal Science
SHERLOCK and HUDSON
The CRISPR-based diagnostic platform SHERLOCK
(Specific High-sensitivity Enzymatic Reporter unLOCKing) uses a programmed
Cas13 enzyme along with reporter molecules to indicate the presence of a
genetic target, such as a virus.
Until now, extracting and isolating nucleic
acids from patient samples was a crucial step in the process that required a
lab and trained personnel, making it difficult to accomplish in the field. Now,
the team has developed a simpler method that allows Cas13 to detect its target
(eg. virus) directly in bodily fluid samples such as saliva or blood.
‘CRISPR-based diagnostic SHERLOCK can detect viruses directly from patient samples and could be used track pathogens during an outbreak.’
The new tool that allows SHERLOCK to do this is called HUDSON, or Heating
Unextracted Diagnostic Samples to Obliterate Nucleases. HUDSON consists of a
rapid chemical and heat treatment that inactivates certain enzymes in the
sample that would otherwise degrade the genetic targets.
The HUDSON processed samples can then be run
through the SHERLOCK procedure. The results of the diagnostic test, positive or
negative, can be easily viewed with the naked eye on specialized paper strips. Moreover, the entire
process can be completed in under two hours.
What does the Sherlock update mean?
The update on SHERLOCK means that now
clinicians will be able to quickly and cheaply diagnose patient samples and
track epidemics such as Ebola
with limited equipment, which was a major barrier to rapid deployment in
SHERLOCK can now be used to detect viruses
directly from clinical samples such as blood or saliva. This eliminates a
processing step that previously required a lab environment and professionally
This is a major advancement which will allow
the use of SHERLOCK in areas where special training and clinical laboratories
can be challenging to access.
Expanding the SHERLOCK platform
related viral species from one another
The team has designed SHERLOCK reagents which
will make it easier and faster to distinguish multiple related viral species
like Zika, dengue, West Nile, and yellow fever
from one another. This will prove useful
when a patient has general symptoms, such as a fever, that could be caused by
more than one pathogen.
A user friendly
The updated platform puts us even closer to a
fast and user-friendly diagnostic that can be easily deployed anywhere.
"With every enhancement to the SHERLOCK
pipeline, the diagnostic process accelerates and requires less equipment,"
says Catherine Freije, graduate student and co-author of the study. "We're
trying to make these tools better and easier to use so that the diagnosis can
move closer to the patient, where it really needs to be."
The platform is capable of identifying clinically
relevant mutations such as a small mutation in Zika
virus that has been associated with microcephaly
The team aims to develop a framework to ensure
the SHERLOCK platform is easily accessible in parts of the world where there is
an urgent need for fast, inexpensive, reliable, field-based diagnostics.
- Field-deployable viral diagnostics using CRISPR-Cas13 - (http://science.sciencemag.org/content/360/6387/444)