Delhi, October 02: Indian scientists have developed a new variant of currently
popular gene editing tool, CRISPR-Cas9, and have shown that this variant can
increase precision in editing genome while avoiding unintended changes in
Findings published in PNAS
researchers have also shown that this type of gene editing can be used to
correct sickle cell anemia, a genetic blood disorder. The
experiments have been done in human-derived cells from patients of sickle cell
anemia, according to findings of the study published
in leading scientific journal Proceedings of the National Academy of
study has been done by researchers from the Delhi-based Institute of Genomics and Integrative Biology (IGIB) of
the Council of Scientific and Industrial Research (CSIR).
By reprogramming and using a
naturally occurring gene editing system – CRISPR-Cas9 – found in bacteria,
scientists globally have been engaged in ‘editing’ genome of various organisms.
CRISPR-Cas9 stands for ‘Clustered regularly interspaced short palindromic repeats and
CRISPR-associated protein 9.’ This protein can be
programmed to go to a desired location in the genome and correct or edit
defective strands (such as those involved in certain diseases) of DNA. The
technology, when perfected, may be used to treat several genetic disorders.
However, the current technique faces challenges as the ‘molecular scissors’
could sometimes miss its target and result in unintentional results.
of the widely used Cas9 enzyme in gene editing is Streptococcus pyogenes
Cas9 (SpCas9) and its engineered variants. They have been harnessed for several
gene-editing applications across different platforms, but concerns remain
regarding their off-targeting at multiple locations across the genome. To
overcome these problems, Indian researchers used another
naturally occurring Cas9 from bacteria called Francisella novicida.
“We have shown that Cas9 from Francisella novicida
(FnCas9) can perform genome editing through homology directed repair and this
can be used for correction of disease causing mutations,” said Dr. Debojyoti
Chakraborty, senior scientist at IGIB, who led the study, while speaking to India
Science Wire. “It has extremely high specificity of DNA interrogation and
does not tolerate mismatches in the target both under in vivo and in vitro
protein (FnCas9) has shown negligible binding affinity to off-targets differing
by one or more mismatches, rendering it highly specific in target recognition,”
the researchers have observed in their study.
technique has been applied to correct DNA derived from patients of sickle cell
anemia. “We demonstrate FnCas9-mediated correction of the sickle cell mutation
in patient-derived induced pluripotent stem cells and propose that it can be
used for precise therapeutic genome editing for a wide variety of genetic
disorders,” researchers said.
research team from IGIB included Sundaram Acharya, Arpit Mishra, Deepanjan
Paul, Asgar Hussain Ansari, Mohd. Azhar, Manoj Kumar, Riya Rauthan, Namrata
Sharma, Meghali Aich, Dipanjali Sinha, Saumya Sharma, Shivani Jain, Arjun Ray,
Suman Jain, Sivaprakash Ramalingam, Souvik Maiti and Debojyoti Chakraborty.
By Dinesh C Sharma
(India Science Wire)
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