geneediting tool CRISPR
which was considered the breakthrough of 2015
suffered a drawback that its gene editing mechanism could not be switched off
to avoid mutations in unwanted regions of the genome.
‘Identification of anti-CRISPR proteins will allow safer use of the CRISPR-Cas 9 system.’
research team from The UC San Francisco has provided an effective
mechanism for switching off this gene editing tool in a new study aimed at
identifying mechanisms that prevent the activity of the CRISPR-Cas 9 system.
CRISPR-Cas 9 system
is a unique technology that allows
scientists to add or delete specific regions of the genome and is considered to
be of potential use in the treatment of genetic disorders. CRISPR stands for
Clustered Repeat Interspersed Palindromic Region and it is used to generate
customized RNA sequences.
Mechanism of Action of
CRISPR-Cas 9 System
There exists a guide
RNA that is present among an RNA scaffold, the RNA scaffold binds to the genome
and the guide RNA molecule binds to the complementary DNA segment. This acts as
a signal for the enzyme Cas 9 to cut the strand of DNA and within this region,
the required sequence of DNA may be added.
the RNA segment should bind only to the
complementary strand of the DNA and aid in adding or deleting segments of the
DNA. However, sometimes there are mutations that are caused at unintended
sections of the DNA. This has led people to be cautious about the use of CRISPR
in the treatment of genetic
newly identified anti-CRISPR proteins will aid in
- A more precise control
over the use of CRISPR
- A method to block any harm caused by
this technique like unwanted mutations
CRISPR gene editing system was identified and obtained from bacteria, which had
developed this system to safeguard itself from invading viruses. As soon as a
virus enters the system, the bacteria would make a copy of the viral genome and
store it in its DNA. When the virus attacks the next time, the CRISPR-Cas 9
system was used to cut the viral DNA and prevent it from replicating.
research team hypothesized that some viruses were able to circumvent this
CRISPR-Cas 9 system effectively and multiply within bacteria, therefore, there
may exist anti-CRISPR molecules, which could be used to turn off the
team felt that the CRISPR gene editing system was "not smart" and that,
ideally, it should cut and edit the very bacterial genome that it was a part
of. Since, it never attacked the bacterial genome, it was evident that there
may be certain elements, which prevented it from doing so.
Experiments on Listeria
is a bacterium that causes foodborne illness
. The research team
studied this bacterium for the presence of anti-CRISPR proteins among strains
that showed CRISPR system attacked the host genome. They identified 4
anti-CRISPR molecules, out of which two of them were found to be effective
against SpyCas9, an enzyme that is commonly used in CRISPR editing tools.
AcrIIA2 and AcrIIA4
and AcrIIA4 were found to be potent in inhibiting the CRISPR-Cas 9 system and the
researchers are looking forward to conducting experiments in human models to
ascertain efficiency. The researchers would also like to continue their
experiments in these anti-CRISPR molecules to understand their mechanism of
action and identify other potential blockers for the CRISPR-Cas 9 system.
anti-CRISPR proteins will be effective in controlling the gene editing system
and can be used to turn the system off to avoid non-specific mutations. There
have been previous studies that have found that such non-specific mutations
could lead to the development of cancer. This has resulted in a failure to use
the CRISPR-Cas 9 system for treating genetic disorders.
scientists believe that with the identification of the anti-CRISPR molecules,
there will be increased use of CRISPR to treat disease conditions. CRISPR is
also used to increase the activity and decrease the activity of certain genes,
without deleting or adding elements to the gene. Such modifications, called CRISPR
interference and CRISPR activation,
can also be carried out in a safer
environment with these anti-CRISPR molecules.
author of the study, Dr. Joseph Bondy-Denomy, a UCSF Sandler Faculty Fellow
added, "Scientists and the public are reasonably concerned about CRISPR being so
powerful that it potentially gets put to dangerous uses. These inhibitors
provide a mechanism to block nefarious or out-of-control CRISPR applications,
making it safer to explore all the ways this technology can be used to help
and its gene editing ability has been a cause for a lot of concern as its use
could potentially alter significant aspects of the DNA. Though there is a lot
of scope for this gene editing tool in the treatment of disease conditions,
scientists have been cautious about using it. The discovery of these
anti-CRISPR proteins will provide a defense mechanism that could restrict any
harmful use of this gene editing tool.
- What is CRISPR-Cas9? - http://www.yourgenome.org/facts/what-is-crispr-cas9)