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CRISPR, a revolution in gene editing


  • Understanding CRISPR and its uses
  • Investing in CRISPR focused biotech stock
  • Risks associated with CRISPR and its future applications

 

Imagine a world where parents can have bespoke kids by selecting their skin colour, height, hair or prevent them from having hereditary disorders or diseases. Farmers can modify crops to make them more nutritious or alter their specific qualities, while someone can create an entirely new species. It sounds like a sequence from a sci-fi movie or a novel, but some of these activities are already happening with CRISPR in the world. 

CRISPR, which is also called CRISPR-Cas9 is a new class of molecular tool to modifying DNA that allows scientists to precisely target and cut any kind of genetic material. It is a revolutionary technology as it is easier to implement, faster, cheaper and contains high accuracy than other traditional methods, including the zinc-finger nuclease (ZFN) technology and transcription activator-like effector nuclease (TALEN), which scientists have ever had to modify and manipulate the code of life; DNA, on any organism on earth. Though the CRISPR technology is at its nascent stage and scientists are experimenting with its application in food, animals and even human therapeutic areas. It has great potential to transform a business from pharmaceuticals to agriculture.

What is CRISPR?

‘CRISPR’ stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are the traits of a bacterial defence system that forms the basis for CRISPR-Cas9 genome editing technology. It is a specialised region of DNA with two distinct characteristics 1) the presence of nucleotide repeats and 2) 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 a simple way, it is a series of short repeating DNA sequences with spacers sitting in between. The bacteria capture the spacers from invading viruses that previously attacked the organism and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays serve as a bank of memories and allow the bacteria to recognise viruses and fight off future attacks. If the viruses attack again, the bacteria produce RNA (ribonucleic acid) segments from the CRISPR arrays (crRNA) to target the viruses' DNA and then use Cas protein-Cas9 or a similar enzyme which act as molecular scissor that cut the DNA apart, which disables the virus. Thus, CRISPR systems consist of a protein with sequence-snipping capabilities and a genetic GPS guide that naturally evolved across the bacteria as a way to remember and defend against invading viruses. When these components are transferred into other organisms, it allows for the manipulation or editing of genes.

Key players of CRISPR technology and how it works?

There are three key elements of CRISPR technology:

1.       CRISPR RNA (crRNA) and guide RNA, each crRNA consists of a nucleotide repeat and a spacer portion. The nucleotide sequence of the CRISPR produces a complementary sequence of single-stranded RNA. Guide RNA is engineered in a lab to locate the targeted gene.

2.       CRISPR-associated protein 9 (Cas9), the enzymes works as molecular scissor that chops out undesired DNA.

3.       Desired DNA, the piece of DNA which is inserted after snipping out undesired DNA.

The CRISPR immune system works in three steps:

a.       Adaption - DNA of an invading virus is processed into short segments that are inserted into the CRISPR sequence as new spacers.

b.       Guiding - once a spacer is incorporated and the virus attacks again, the CRISPR is transcribed and processed into short single-stranded RNA sequences called CRISPR RNA or crRNA that is capable of guiding the system to matching sequences of DNA.

c.       Targeting - when the target DNA is found, Cas9 binds to the DNA and cuts it, snipping the targeted gene off. Using modified versions of Cas9, scientists can activate gene expression instead of cutting the DNA.

While there are many Cas enzymes, the widely-known term CRISPR-Cas9 refers to a Cas9 variety being the best enzymes used to dissect animal and human DNA.

CRISPR’s applications

1.       In Industry and agriculture: CRISPR is advantageous for industries that use bacterial cultures to prevent viruses, which infect and damage the quality and quantity of food. Hence, by using CRISPR technology, manufacturers can improve culture sustainability and lifespan. The United States Department of Agriculture (USDA) approved production of CRISPR edited food by declaring it as an ‘accelerated form of selective breeding.’

2.       In gene therapy and lab application: CRISPR technology has already shown potential in editing plant genomes and even human cells. Moreover, changing sequence or editing even one gene can significantly affect the biology of cell and CRISPR technology allows scientists to modify specific genes and make precise changes in genes of organisms. This process allows a scientist to make an animal model to study the progress and treatment of human diseases.

3.       In medical application: after getting success in a lab, many scientists are looking forward to the use of CRISPR technology in medical science, especially in curing genetic diseases. In addition, scientists are researching to use CRISPR to treat rare diseases such as Cancer and Huntington’s disease.

Investing in CRISPR tech

The global market for CRISPR-Cas9 tech is expected to reach $5.3 billion by 2025 from $1.2 billion in 2017, growing at 20% CAGR (Source: Ahead Intel). While gene editing technologies are showing the potential to ignite a revolution in healthcare, but only three companies are listed and available for investing in this technology publicly. All these three companies; Editas Medicine, CRISPR Therapeutics, and Intellia Therapeutics are working on drugs related to CRISPR in various stages for different human diseases. All went public through an IPO in 2016, though, well-funded by investors before a series of funding rounds, apart from one private company Caribou Biosciences. Thereafter, all these CRISPR-focused biotech stocks gave a good return to investors. Academic Institution from the US and China are actively pursuing research activities in CRISPR domain backed by their governments. While NIH (National Institutes of Health, the USA) has funded 6,685 CRISPR related research project worth $3.08 billion from 2011 to 2018 (Source: NIH RePORTER), National Natural Science Foundation of China, a Chinese government-backed institution has awarded more than 23 million yuan ($3.5 million) to at least 42 CRISPR projects in 2017.

Limitations, risks and controversies

1.       Off-target effects and mosaic generation: the major risk of using CRISPR technology is off-target activity i.e. change or mutation might be induced in a healthy genomic core that was not targeted instead of undesired DNA. Another concern is a mosaic generation which can occur after a CRISPR treatment and patient could have a mix of both edited and unedited cells called mosaic, which may cause some cells to get unrepaired, while others might repair. Furthermore, such mutation and therapies can also trigger an undesired response from a patient’s immune system.

2.       Illegal human genome editing: CRISPR technology allows editing of a genome, which mean one could design his/her kids or pets. Further, any mutation in the germline cell will be passed on to generations, hence, it is important to deploy ethical guidelines for its implementation. While human germline editing is currently illegal almost everywhere, China has recently defied international norms and edited the DNA of three children to make them HIV resistant.

3.       Ecological risks: manipulating nature with CRISPR by changing plant pollution, animals and other species may have consequences for the ecosystem that could be unforeseeable and dire. Concerns have been raised for using this technique to bring back extinct species could bring more harm than good.

4.       Biohackers and use at home: since CRISPR technology is cheap and easy then other gene editing technologies, there is a risk of uncontrolled use of this in home-based labs. For example, a biohacking start-up, The Odin, sells DIY Bacterial CRISPR kits on its website for a retail price of $159, which is easy on the pocket.

The Future of CRISPR

CRISPR is the first technology that is truly capable of changing the fundamental chemistry of who we are. This revolutionary technology has already disrupted the way genome editing is done and has a great potential to transform the future medicine and the way of treatment for any disease. Currently, it is being directed mostly towards food tech and therapeutic areas, the use of CRISPR technology is limitless. The CRISPR system enables unprecedented and unrivalled control over genes by modifying a targeted DNA sequence. Thus, allowing an easier way to develop genetically modified species, while also raising the requirement of new regulation to address its menace.

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