How is the tool different from other editing systems? Is there a possibility of the tool being misused?

The story so far: The 2020 Nobel Prizes for sciences announced this week made history of sorts when one of it was exclusively shared by two women. Scientists Jennifer Doudna and Emmanuelle Charpentier bagged the Nobel Prize for Chemistry for the development of a method for genome editing. The discovery of one of gene technologys sharpest tools: the CRISPR/Cas9 genetic scissors will lead to the emergence of novel biological applications by making it easier to edit genes, and may make the dream of curing inherited diseases come true.

Much like what Microsoft (MS) Word does for writing, the CRISPR/Cas9 system allows for adding, altering and deleting the genomic code in living beings. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are pieces of DNA that bacteria snip off from viruses that once attacked them, much like file names used to store various documents we write in MS Word.

The COVID-19 pandemic has brought to the fore the importance of memory cells, which can quickly produce relevant antibodies to neutralise a repeat infection by a virus. Similarly, the CRISPR are a part of bacterias immunological systems that help them in recognising threatening viruses. When they sense a lurking virus, the bacteria produce customised RNA, which is necessary to translate DNA into protein, gleaned from the CRISPR libraries. This also contains Cas (CRISPR-associated) genes that are used to produce enzymes such as Cas-9. These enzymes the Cas-9 being a particularly popular one can be used to chop the DNA of the virus and destroy them.

Using the tool, researchers can change the DNA of animals, plants and microorganisms with precision. Emmanuelle Charpentier, who is now director, Max Planck Institute for Infection Biology, Berlin, had studied Streptococcus pyogenes, a species of bacteria known to be associated with a range of illnesses such as pharyngitis, tonsillitis and scarlet fever. While studying this, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacterias ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA, the Nobel release explains. Dr. Charpentier published her discovery in 2011. The same year, she initiated a collaboration with biochemist Jennifer Doudna, now a professor at the University of California, Berkeley.

Together, they succeeded in recreating the bacterias genetic scissors in a test tube and simplifying the scissors molecular components so they were easier to use, says an explainer on the Nobel Prizes website on their work. In a significant experiment, they reprogrammed the genetic scissors. In their natural form, the scissors recognise DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. Where the DNA is cut it is then easy to rewrite the code of life, the note adds.

Also read | What is genome editing

Other genome editing systems like TALENs and Zinc-Finger Nucleases can do similar jobs, but several users consider the Charpentier-Doudna tool more adaptable and easier to use.

It is less than a decade since this system gained wide research and commercial interest, but in the past few years, scientists have been able to make precise single-base-pair changes or larger insertions. Coupled with the availability of genome sequences for a growing number of organisms, the technology allows researchers to find out what genes do, move mutations that are identified and associated with disease into systems where they can be studied and tested for treatment, or where they can be tested in combinations with other mutations.

Editorial | Scissoring the DNA

The commercial potential of the system is so compelling that within years of its development, there was a battle over the ownership of the intellectual property rights of the CRISPR/Cas9 involving the University of California and the Massachusetts Institute of Technology's Broad Institute. The essence of this was that Feng Zhang of the Broad Institute had discovered a way to deploy the system in eukaryotic cells (that make up animal cells), whereas Dr. Doudnas patent application covered the process more generally. Dr. Zhangs patent was granted before Dr. Doudnas application. The patent dispute is still ongoing, and both sides claim victory in terms of the commercial application of the patents.

Also read | CRISPR-Cas gene editing causes crisper debates

The prize to CRISPR/Cas9 may be unusual as it is rare for a method to be announced and conferred a Nobel within a decade of its discovery, but it underlines its game-changing potential. In the last five years, both Dr. Doudna and Dr. Charpentier have been recipients of several important prizes in sciences.

Earlier this year, a person with hereditary blindness became the first to have a CRISPR/Cas-9-based therapy directly injected into her body. Gene-editing company CRISPR Therapeutics announced in June that two patients with beta thalassemia and one with sickle cell disease would no longer require blood transfusions after their bone marrow stem cells were edited using CRISPR techniques.

Earlier this week, according to a report in Chemistry World, Dr. Doudna launched a new company, Scribe Therapeutics, to begin work on treatments for amyotrophic lateral sclerosis. Reuters reported that Dr. Doudna is already employing CRISPR in the battle against the COVID-19 as a co-founder of biotech startup Mammoth, which has tied up with GlaxoSmithKline to develop a test to detect infections.

This year, the CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) in Delhi developed a COVID-19 testing kit, nicknamed Feluda, after the fictional Bengali detective, based on the CRISPR/Cas9 system. There are commercial CRISPR-based home kits that allow amateur researchers to develop their own biotechnology applications, triggering a sub-culture called bio-hacking.

Also read | Change in ICMR rules stalls COVID-19 test kits from government labs

Research is already underway for using proteins that are smaller and more efficient than Cas-9, though the system purportedly holds promise for treating more complex diseases, such as cancer, heart diseases, mental illnesses, and the human immunodeficiency virus (HIV) infection.

The most controversial application of CRISPR/Cas9 was in 2018, when Chinese researcher He Jiankui announced that he had used it to create gene-edited twins Lula and Nana via in-vitro fertilisation. He used the gene scissors on the children when they were embryos to edit a gene, CCR5, that in its modified form would ostensibly protect the babies from HIV. The HIV uses the CCR5 to infect cells and the modified gene would shut the door against such an entry. He was widely condemned and sentenced to three years in jail, and stripped of his position at Shenzhen University, where he worked.

Also read | How safe is CRISPR?

While he broke a number of medical rules, what is particularly controversial is that the specific mutations that would supposedly protect the children from HIV were not achieved. There were a host of other unintended mutations too. It is not known how these mutations are going to play out over the children's lifetimes and whether they will spread to humanity more widely in due course. Thus, even though the CRISPR/Cas-9 system allows a democratic usage in labs across the world to tinker with genomes, it still has not reached the level of precision required to be sure that it does not cause unintentional side effects.

This year has seen a remarkable representation of women. Four women have been named Nobel Laureates in 2020 against five men so far. The Sveriges Riksbank (Swedens national bank) Prize for economics, or the 'economics Nobel', will be announced next week. The 2001-2019 interval has seen the maximum number of women Laureates 24 compared to just 11 from 1981 to 2000 and 7 from 1961 to 1980. There were only 12 women Laureates from 1901 to 1960. Only one woman, Marie Curie, has been honoured twice, with the 1903 Nobel Prize in Physics and the 1911 Nobel Prize in Chemistry.

Many women think that no matter what they do, their work will never be recognized the way it would be if they were a man, Al Jazeera quoted Dr. Doudna as saying. And I think (this prize) refutes that. It makes a strong statement that women can do science, women can do chemistry, and that great science is recognised and honoured.

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The Hindu Explains | How does a genome editing tool developed by two women scientists help in tackling diseases? - The Hindu

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