One of the most celebrated findings of the scientific community is genome editing by CRISPR-Cas9. Genome editing or gene editing refers to the process of altering an organism’s DNA. Similar to addition and subtraction, DNA is also subjected to these mathematical principles through the gene editing technology. This revolutionary technology is more accurate, economic, efficient and quick as compared to other gene editing technologies. Scientists Emmanuellle Charpentier and Jennifer Doudna were awarded the Nobel prize in 2020 for developing CRISPR-Cas9 gene editing.
What is CRISPR and How Does it Work?
CRISPR is the short form for ‘Clustered Regularly Interspaced Short Palindromic Repeats.’ They are naturally found in bacteria as a part of their immune defence system. The CRISPR system provides a safety net to bacteria against viral infections. The modus operandi of CRISPR in bacteria is the destruction of viral DNA that is injected into the bacteria, through virus during infection, by an enzyme called Cas-9. This clever system of bacteria was adapted by scientists to create a powerful gene editing tool. A target DNA sequence (DNA to be altered) is used to design a custom RNA guide that matches with it. This guide RNA is attached to Cas9 and inserted into the genome. Precise cuts are made by Cas9 that is guided by the RNA to the location of DNA sequence that is to be modified allowing DNA fragments to be deleted, altered or inserted accordingly.
The working mechanism of CRISPR-Cas9 system. A target sequence to be altered is chosen from the dsDNA. Guide RNA (gRNA) guides Cas9 to the target and makes appropriate cuts.
Applications of CRISPR
CRISPR-Cas9 works as genetic scissors for gene editing and has paved a way in potentially solving some of the major crises in the world. The said impacts indicate a boost in the agriculture field through the development of superior crops resistant to pests and diseases while providing high yield and nutritional value. Similarly, in the field of medicine, it is capable of being used as probable treatment for genetic diseases such as cystic fibrosis, haemophilia and sickle cell anaemia. Furthermore, customised treatment plans can be curated for cancer patients. This gene editing technology does not limit to humans as there is room for improved health and productivity in livestock too. The world of scientific research has advanced leaps and bounds, thanks to CRISPR-Cas9. It is currently employed in genetic studies by switching the genes on and off, like electrical switches, in stem cells, organoids and animal models and studying their impact on health and disease.
The mode of action of Casgevy gene therapy. The blood forming stem cells are harnessed from the patient, edited for a gene and transferred back into the patient. Healthy RBCs are produced. Image source BBC.
Success Stories
Continuing the incredible feats of CRISPR-Cas9 gene editing, we recently saw a science fiction level treatment being approved for treating sickle cell anaemia. Casgevy is ‘first-of-its-kind’ gene editing drug to restore healthy haemoglobin in sickle-cell disease. The bone marrow stem cells responsible for making faulty haemoglobin and sickle-shaped red blood cells are extracted from the patient. These cells are genetically modified by turning the BCL11A gene off using CRISPR-Cas9 and transplanted into the patient again where they produce healthy haemoglobin and normal red blood cells. Similarly, another cell-based gene therapy called Lyfgenia is approved by FDA for treating sickle cell patients aged 12 years and older. Its principle is quite different from that of Casgevy. A viral envelope is used as a gene delivery vehicle to transport healthy haemoglobin in the extracted blood stem cells from the patients. Once the delivery is complete, the cells are transferred back into the patient where they start making normal RBCs. We see a ray of hope for developing therapies to treat other genetic diseases.
Ethical Considerations
The fruits of exploiting CRISPR-Cas9 gene editing are diverse and sweet. The possibilities seem endless when thinking of the future, but one has to question its limitations and the potential negative impacts it can amount to at present and in the coming days. DNA editing results in permanent change in the genome therefore can change characteristics like eye colour, hair colour, blood type, etc. These traits can be inheritable. Hence at some point, we might see the human tendency of being creative in using technology strike in and things can take a very dark turn. The world is given a choice to eradicate diseases, mental disorders or particular genetic traits or to keep them. A dangerous idea of creation of a superior human race might be lurking around the corner of the 21st century. Even though genetic engineering was established for the betterment of humanity, it can easily control humanity as it is hard to resist the tempting options it provides – strong humans free from diseases, designer babies by bioengineering of children, continuing a certain trait in future generations, etc.
Digging in deeper, CRISPR-Cas9 gene editing has shown off-site targeting resulting in mutations. These mutations can be inheritable and humanity might develop unwanted traits and characteristics. Germline editing can have threatening consequences in human beings both physically and socially. Mutations eventually lead to creation of novel diseases with no known cure. In a social setting, it will be a crime to give birth to children with disabilities in the future. Children will be assessed in terms of quality. Humans will have failed to create a better world for their children, instead there will be a competition to create perfect children for the existing world by then. This pioneering gene editing technology can be used in modern day eugenics. However, this eugenics will be velvet-like as it will hide behind the facade of science and terms like ‘freedom’ and ‘choice’ of the people while roaming freely in the world. We will be left with a whole package of new diseases, trauma, stress and twisted reality of complete acceptance of these terrifying notions and practices.
Where Are We At Present?
In 2023, the Third International Summit on Human Genome Editing concluded that human germline editing with heritable traits for procreation ‘remains unacceptable.’ This statement is a reflection of lack of governance frameworks, policies, ethical margins in place to ensure the safe practice of human embryo editing. The notion of CRISPR babies that came into light through Chinese scientist He Jiankui in 2018 left the world appalled. He announced that he produced genetically edited babies by modifying a significant gene to accord HIV resistance in the babies. With the characteristic of HIV resistance in He’s CRISPR babies being transferrable to the future generations, it is crucial that the gene editing technology has to be errorless or has high efficiency. However, this is yet to be determined given the clear drawbacks of the technology. The twins delivered by He may showcase mosaicism where the cells end up getting varied edits and can result in enhanced susceptibility towards diseases that are lethal. This feat has drawn on the current state of human germline genome editing being restricted to research. It is fairly safe to say that humanity is sheltered for now owing to this germline editing limitation.
Thus to conclude, the advent of gene editing by CRISPR-Cas9 has brought a new dawn in the history of humanity. It has broadened our horizons in terms of devising novel therapeutic approaches for genetic diseases, complete annihilation of such disorders and food quality. Taken from bacteria, this system has shown the world a small peek of what is to come in the form of gene editing drugs. As much appealing as this technology sounds, it possesses a threat to humanity. It can become a means for eugenics to rise again leaving a significant imprint on our genetic and social status. In the end it all comes down to where the ball will be dropped, should it be dropped in the right court, we can witness an irrevocable positive advancement in our quality of lives and surroundings through this technology.
Deeksha, is a Biochemist and an aspiring neuroscientist. Her research interest lies at the intersection of molecular neuroscience and drug discovery.
[…] species that would resemble the mammoth and survive in Arctic climates. With the introduction of CRISPR gene-editing technology, precise alterations to an organism’s genome can be made, allowing the scientists to add, remove, […]
Comments are closed.