CRISPR CAS9

CRISPR CAS9
CRISPR CAS9

Genes contain the bio-information that defines all living. Physical attributes like height, skin or hair colour, more subtle features and even behavioural traits can be attributed to information encoded in the genetic material. Gene editing is the ability to alter this information which gives scientists the power to control some of these features.

CRISPR CAS9 is the newest gene-editing technology that can be used for the purpose of altering genetic expression or changing the genome of an organism. “CRISPR” stands for “Clusters of Regularly Interspaced Short Palindromic Repeats.” It is a specialized region of DNA with two distinct characteristics: the presence of nucleotide repeats and spacers. Repeated sequences of nucleotides— the building blocks of DNA— are distributed throughout a CRISPR region. Spacers are bits of DNA that are interspersed among these repeated sequences.

In 2012 the scientists found the CRISPR as a part of the immune system. For instance, when a virus attacks a bacteria, it fights back by cutting the virus DNA. In the process it stores some of the DNA. The next time there is an invasion, the bacteria produces an enzyme called CAS9 which matches the stored fingerprints with the invaders. If it matches, CAS9 snips the invading DNA. Thus, the CRISPR CAS9 gene editing tool has two components:

  1. A short RNA sequence that can bind to a specific target of the DNA.
  2. CAS9 enzyme which acts as a molecular scissors to cut the DNA.

To edit a gene, the short RNA sequence that perfectly matches the DNA sequence is introduced. Once it binds to the DNA, the CAS9 enzyme cuts the DNA target where the RNA sequence is bound. Once the DNA is cut the natural repair mechanism is utilised to add or remove genetic material to make changes to the DNA.

The CRISPR technology can have the following applications:

  1. CRISPR CAS9 has also been seen as a promising way to create potential genome editing treatments for diseases such as HIV, cancer or sickle cell disease. Such therapeutics could inactivate a disease-causing gene or correct a genetic mutation which could potentially cure inherited diseases, such as some forms of heart disease and cancer, and a rare disorder that causes vision loss.
  2. CRISPR gene editing provides for the ultimate toolbox for genetic manipulation. CRISPR systems are already delivering superior genetic models for fundamental disease research, drug screening, and therapy development, rapid diagnostics, in-vivo editing and correction of heritable conditions. Scientists are working on the theory that CRISPR might be used to boost the function of the body’s T-cells so that the immune system is better at recognizing and killing cancer. Disorders of the blood and immune system are other potential targets.
  3. In agriculture, this technique can create plants that not only produce higher yields, like Lippman’s tomatoes but also ones that are more nutritious and more impervious to drought and pests, traits that may help crops endure more extreme weather patterns predicted in the coming years.

However there has been genuine concern about the technology because:

  1. Many prominent scientists and doctors have questioned the safety and efficiency of CRISPR CAS9 and there have been concerns that it may cause off target mutations and mosaicism. In the former situation CRISPR could miss the target gene and attach itself to another similar sequence thereby creating properties far different from those intended ones. In the latter situation of mosaicism CRISPR CAS9 could target well after the DNA sequence of some and not all of the necessary cells. This may lead to genetically distinct cells, whereby some cells may still carry deadly mutations, rendering the treatment ineffective.
  2. In 2 different studies conducted by Kardinska Institute, Sweden and the other by the biopharmaceutical company Novartis highlighted that CRISPR CAS9 edited cells might trigger cancer. The studies showed that CRISPR CAS9 system induced activation of a protein called P53. The P53 protein acts as a guardian/gatekeeper in the cells to keep them healthy and prevents them from turning cancerous. In many cancers, the cells lose their ability to repair deleterious genes due to an impaired P53 function. The study claims that a functional P53 swings into action in the targeted cell and repairs the edited site rendering the CAS9 mediated site ineffective. In cells where editing is adequate, P53 may be dysfunctional. In simpler words P53 and CAS9 mediated editing cannot coexist.
  3. In an another study it was highlighted that off target effects may not be sufficient to identify adverse effect sites. A comprehensive genomic analysis of edited using long-read DNA sequencing technology is required.
  4. Bioethicists fear that the abuse of gene-editing may be used by not only misguided governments but also by private sector to develop ‘superior’ race or commoditise the technology to produce the perfect child.

Human civilization has progressed by interfering with the natural evolutionary process. In this process, the application of Gene Editing is inevitable. In this sense, CRISPR technology is indeed a path-breaking technology, to alter genes in order to tackle a number of conventional and unconventional problems, especially in the health sector. However, to prevent it from being a disruptive force, it is better to regulate it.

India does not have a comprehensive gene editing policy in place, though germline gene editing is banned in line with international norms. Yet, in the face of persisting diseases and crippling human conditions, divine intervention may sometimes need to be supplemented with genetic ones in a carefully regulated environment.

The process of modernising existing governance frameworks should be complemented with public engagement efforts aimed at closing knowledge gaps and building scientific literacy among non-expert audiences. This will ensure safe, secure and ethical use of biotechnology for societal needs.

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