In simple terms, genome editing (also referred to as gene editing) is a set of technologies that can be used to modify the DNA of a cell or an organism. Genome editing uses an enzyme (also called as engineered nucleases) to make cuts at specific DNA sequences, which when repaired by the cell, results in a change or edit made to the sequence.
Over the years, researchers have sought new methods to modify DNA sequences and their genetic functions easily. Among its most practical applications, genome editing has the potential to correct genetic defects, improve crop yields, and prevent the spread of human diseases.
Pronounced as “crisper”, the CRISPR genome editing technology is among the recent developments and was first published in a 2007 research paper, where researchers who were working on the Streptococcus thermophilus bacteria found new spacers incorporated in the CRISPR region following a virus attack. Since then, rapid research and development in this field have generated considerable excitement in the scientific research community as a useful mode of gene editing, as compared to other gene editing techniques.
So, how does the CRISPR gene editing technology work and how can it impact the Healthcare industry?
What is CRISPR?
Short for Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR or the CRISPR-Cas9 technology was adapted from the natural defensive genome editing process found in bacteria. The CRISPR-associated protein or Cas9 is an enzyme that works like a molecular scissor to cut DNA strands.
How do bacteria and other micro-organisms perform genome editing and why? Here is how and why they do that:
These micro-organisms, when attacked by viruses or other foreign bodies, capture the DNA snippets from the invading bodies and use them to create DNA segments, also called as CRISPR arrays. CRISPR arrays enable the bacteria to remember the attacking viruses. In the event of a repeat attack from the same virus, the bacteria use the CRISPR arrays to produce RNA segments, which are then injected into the virus’ DNA. The CRISPR-associated protein or Cas9 is an enzyme that is used to cut the foreign DNA and disable the virus.
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Based on the above methodology, the CRISPR technology has been developed on similar lines in research laboratories. The CRISPR genome editing technique uses a small RNA piece to be attached to the target DNA sequence in the genome. The RNA is also bound to the Cas9 enzyme. Just like the bacteria, the modified RNA recognises the DNA sequence, while the Cas9 enzyme cuts the DNA at the target location.
Industry Potential of the CRISPR Genome Editing Technology
The global market for the CRISPR genome editing technology has grown to around $487 million for the year 2017 and is projected to increase to about $7.9 billion by the year 2026. While North America is the dominant market for this technology, the Asia Pacific including India is projected to be the fastest growing market.
Genome editing using the CRISPR technology is showing great potential in the prevention and treatment of human diseases. While the current lab research is being conducted on animal models, researchers and scientists are evaluating on making this technology safe for human beings.
This technology also holds promise in the research of genetic disorders and conditions such as cystic fibrosis, haemophilia, cataracts, and sickle cell diseases. An additional potential of this technology is in the treatment of complex ailments including heart diseases, mental illness, and HIV infections.
Apart from its application in medical treatments, CRISPR technology has enormous potential in the following industry domains:
- Agriculture: to improve crop yields, produce more nutritious food and improve drought and disease resistance in plants. For instance, the Innovative Genomics Institute is partnering with the candy company, Mars to use CRISPR technology to produce disease-resistant cacao.
- Food preservation: to potentially replace traditional food preservatives and provide better food preservation measures following the harvest. In 2016, the white button mushroom was the first CRISPR-modified food to be approved by the U.S. Department of Agriculture.
- Beer brewing: to brew hop-less beer and generate superior yeast strains. The bioengineering company, The Odin is selling a home kit for beer manufacturers to use CRISPR technology to produced fluorescent yeast for creating glowing beer.
- Pets and Veterinary industry: to genetically engineer the look of pets, along with providing veterinary services such as preventing the spread of swine diseases and control animal breeding. Although the project is now shut down, the first CRISPR-modified dogs with more muscle power and running abilities were created in China in 2015.
- Biotech industry: for new and improved drug discovery, along with applications in industrial and agricultural biotech. The pharmaceutical company, Bayer AG is partnering with CRISPR Therapeutics to develop new drugs.
- Biofuel industry: for an oil-rich strain in algae that can be potentially converted into biofuel. Scientists at Synthetic Genomics and Oil company, ExxonMobil successfully created this biofuel in June 2017.
How the CRISPR Technology is Disrupting the Healthcare Industry
CRISPR technology has the potential to transform or disrupt the following five healthcare verticals:
1. Cancer Treatment
CRISPR technology is being explored by cancer researchers in the potential engineering of the T-cells or immune cells to locate and destroy cancer-causing cells. To achieve this, cancer patients must be injected with these modified T-cells that can fight cancer. Genome editing company, CRISPR Therapeutics is working on cancer therapy, while Editas Medicine is partnering with cancer treatment company, Juno Therapeutics to develop cancer drugs.
2. Genetic Disorders
Researchers are exploring the potential of CRISPR technologies to treat genetic disorders such as diabetes, cystic fibrosis, and genetic blindness. Typically, most genetic diseases are caused by an improper mutation in a DNA sequence that is responsible for performing a specific function. Identifying these faulty genes and repairing them using CRISPR can potentially cure the corresponding disorder. CRISPR Therapeutics and Vertex plan to jointly develop and commercialise CRISPR technology for Sickle cell disease and Thalassemia.
Research work is carried out to explore the genetic aspects of infertility. A human embryo study conducted by Francis Crick Institute successfully used CRISPR to stop genes from producing the OCT4 protein that results in embryo collapsing, thus leading to miscarriages.
CRISPR-based diagnostic kits can be used to eliminate the need to extract biological samples from patients for diagnostics. Scientists have developed a CRISPR protein, which targets the RNA instead of DNA, thus providing a cheaper and faster tool to diagnose many diseases. Among the pioneers in CRISPR technology, Mammoth Biosciences is using CRISPR technology to create a paper-based diagnostic test, where a human sample can be applied to a detection card to produce visible colour change.
5. Organ Transplantation
Being similar in size and functions to human organs, pig organs can be used for human organ transplantation. To make it safer, CRISPR tools are being used to remove 25 harmful retroviruses from the pig genome to be used in organ transplants.
Start-up company, eGenesis is using gene editing tools to explore the potential of xenotransplantation, a transplantation process of live cells or organs from animals to humans.
Challenges for CRISPR Technology
Despite its enormous industry potential, CRISPR technology does have its share of challenges, including:
- Ethical Challenges: Currently, genome editing techniques including CRISPR are limited to somatic cells, which only affect selected tissues, and the genome changes are not passed on to the next human generation. Modifications made to germline cells such as egg and sperm cells can be inherited by the next generation, raising ethical concerns on the use of technology to enhance desirable human traits such as intelligence and height.
- Human Embryo-related Challenges: Researchers working on eradicating the HBB gene from the human embryo discovered off-target or unintended mutations in the genome when used with the CRISPR technology. These mutations could potentially cause cell deaths or transformations.
DNA mapping or sequencing techniques such as the CRISPR-based genome editing holds tremendous potential in multiple areas including disease control, crop production, and as a safe food preservative.
Along with its impact on the healthcare verticals, researchers are applying the benefits of CRISPR technology in other domains despite the significant challenges and concerns.