The gene-editing tool known as CRISPR is fast becoming known for its potential to treat disease by snipping genetic mutations from DNA.
But genomic
tools like CRISPR also have other possible capabilities, such as the ability to
screen people for the presence of viruses, like dengue and Zika, as well as
debilitating diseases like Parkinson's.
"I think the public perception of CRISPR is very focused on the idea of using gene editing clinically to cure disease. This is no doubt an exciting possibility, but this is only one small piece," said Neville Sanjana, of the New York Genome Center and an assistant professor of biology, neuroscience and physiology at New York University. [10 Amazing Things Scientists Just Did with CRISPR]
"With CRISPR, I think you'll see many applications in synthetic biology," like sensors for pathogens, Sanjana told Live Science.
A natural defense system
At its core,
CRISPR is a natural defense system that evolved in single-celled microorganisms
to fight against invading viruses. The fight is an all-out war. Scientist
estimate that for every cell on Earth, there are about 10 viruses, all
launching relentless missions to replicate themselves by inserting their DNA
into the machinery in cells.
Bacteria use an
arsenal to fight back, including CRISPR, which is an array of short, repeated
sequences of DNA that are separated by spacers that have unique sequences.Bacteria
use it when they are infected with a virus. As the virus's genetic bits
replicate inside the bacteria, CRISPR steps in, guiding the bacterial defenses
toward the foreign material.
The protein in
CRISPR cuts up the intruder, but also collects a short DNA sequence from the
invader, which the protein inserts it into the bacteria's CRISPR as a spacer.
Each time a virus invades and is destroyed, a new spacer gets added to the
CRISPR.
In a sense, the
spacers in CRISPR are an account of the bacteria's battlefield wins, like kill
marks in the stock of a rifle barrel. But the spacers provide another function.
When a virus
that was previously defeated tries to invade, the bacteria recognizes it and
sets about chopping the invader up into tiny bits. And when the bacteria itself
multiplies, it passes it's defense system on to its daughter cells.
"It turns
out you can actually leverage these properties to potentially develop a very
sensitive diagnostic device" that could detect small amounts of molecules
from viruses in human blood, such as Zika virus, said biochemist and CRISPR
expert Sam Sternberg, the group leader of Technology Development at Berkeley,
California-based Caribou Biosciences Inc., which is advancing new applications
for CRISPR-based technologies. [5 Amazing Technologies That Are Revolutionizing
Biotech]
One of the most
recent CRISPR advances in this area is a tool called SHERLOCK (which stands for
Specific High Sensitivity Enzymatic Reporter UnLOCKing). In April 2017, a team
of researchers led by bioengineer James Collins and CRISPR pioneer Feng Zhang
of the Broad Institute of MIT and Harvard reported in Science that they had
programmed a CRISPR molecule to seek out strains of Zika and dengue viruses in
blood serum, urine and saliva and cut them up.
The researchers
programmed the CRISPR molecules to release a fluorescent signal when they were
chopping away at the viruses, so that the presence of the virus could be
detected. SHERLOCK was so sensitive, it was able to distinguish the American
strain of Zika from the African strain and differentiate one strain of dengue
from another one.
Collins and his
team were able to see the presence of the viruses even in extremely low
concentrations, as low as two molecules in a quintillion.
In a separate test,
SHERLOCK was able to detect two different strains of the antibiotic-resistant
superbug Klebsiella pneumoniae. [6 Superbugs to Watch Out For]
Then, in June
2017, a team at the University of Central Florida reported in the journal
Scientific Reports that they had used a CRISPR system to detect the presence of
Parkinson's disease. This disorder of the central nervous system causes
malfunction and death of nerve cells in the brain, and gets worse over time,
causing tremors and problems with movement. The disease affects about 1 million
people in the United States, according to the Parkinson's Disease Foundation.
Although the
cause is unknown, the amount of a protein called alpha-synuclein, normally
found in the brain, rises in people who develop the disease. The researchers
used CRISPR to edit the gene that makes the alpha-synuclein protein so that the
protein would fluoresce. The larger the amount of the protein, the stronger the
fluorescent signal.
The scientists
said they think they could use this technique to test out new drugs to treat
Parkinson's disease.
"If we take
one of these modified cells and treat it with a particular drug, if it doesn't
produce light anymore, then this means the drug is a potential treatment for
this disease," study co-author Sambuddha Basu, a postdoctoral researcher
at Central Florida, said in a statement.
It's still the
very early days for these and other CRISPR-related biological tools, and
because of the diversity of the immune systems in bacteria, it's quite possible
that other tools remain to be discovered, Sternberg said.
"I think it's a really nice example of yet another basic science discovery that has led to a potential breakthrough technology," he said.