The Future of CRISPR: Five Ways to Change the World

Release date: 2018-02-07

Founded in the early 1990s and first used in biochemical experiments seven years later, CRISPR has quickly become the most popular gene editing tool among researchers in the fields of human biology, agriculture and microbiology. Scientists are still exploring how to use CRISPR to change the early stages of the world. Of course, the ability to change DNA (the source code of life itself) has also brought many ethical issues and concerns. With this in mind, there are some of the most exciting applications of this revolutionary technology, and the obstacles that may slow or prevent it from reaching its full potential.

1.CRISPR can correct genetic errors that cause disease

Hypertrophic cardiomyopathy (HCM) is a heart disease that affects approximately one in every 500 people worldwide. The onset of this disease is painful and often fatal. Some dominant gene mutations can cause hardening of the heart tissue, which can lead to chest pain, weakness, and even more severe cardiac arrest. Thanks to recent medical advances, the average life expectancy of patients with HCM is close to that of the average person, but if left untreated, it can lead to life-threatening conditions.

But in the future, we may be able to completely cure the disease through genetic editing. In the summer of 2017, scientists at the Oregon Health and Science University in the United States deleted a defective gene in human embryos using CRISPR. The results were exciting: 36 out of 54 embryos using CRISPR-Cas9 technology within 18 hours of fertilization showed no signs of genetic mutations (nearly developing a chance for the disease), while 13 embryos were only Partial mutation (50% probability of hereditary HCM).

Non-target gene mutations and chimeras (only a few cells change, meaning that a small number of people will genetically mutate) exist only in 13 of the 54 embryos. To further reduce the possibility of partial cell changes, the researchers conducted another experiment in which they directly corrected the same genes in the embryo during fertilization. They found that only one embryo had non-target gene mutations and chimeras. This is an impressive result, making this study more efficient than similar research.

The first author of the study, Shoukhrat Mitalipov, a researcher at the Oregon Health and Science University, said at a news conference: "With this technology, we have the potential to alleviate this genetic disease. The burden on the family and the entire human race." Capturing mutations in the early stages of embryonic development can reduce or even eliminate the need for treatment in later life.

Although some stem cell scientists question whether these dozens of mutations are really repaired, this study does help scientists better understand the efficacy of CRISPR. In addition, one of the co-authors of the HCM study has expressed interest in applying the same technology to specific genetic mutations (BRCA1 and brca2) that increase breast cancer risk.

That is to say, scientists know that changing the genetic code of human embryos may have unintended consequences. What happens if CRISPR makes a mistake in the wrong place, inadvertently changing or removing healthy genes? What effect does this have on patients? In some parts of the world, scientists can be largely unbounded to humans. Embryos were tested. But this is not the case in the United States, Canada or the United Kingdom.

In the United States, the Food and Drug Administration (FDA) does not currently consider the use of public funds to study genes that can be inherited (the Oregon researchers' research was not conducted for implantation, and the research was privately funded). In Canada, editing a gene that can be passed on to future generations is a criminal offence with a maximum penalty of 10 years imprisonment. At the same time, the British Human Fertilization and Embryology Authority authorized a team of scientists in London in 2016 to allow them to edit human embryonic genes. British scientists hope that this will set a precedent and open the door for future applications.

2.CRISPR can eliminate microorganisms that cause disease

Although the treatment of AIDS has turned the virus from a deadly killer into a health threat, scientists have yet to find a cure. This situation may change as the CRISPR technology advances. In 2017, the Chinese research team succeeded in enhancing the resistance of mice to HIV by replicating a genetic mutation that effectively blocks the entry of viruses into cells. Currently, scientists only perform these experiments on animals, but there are reasons to believe that the same method is also applicable to humans. HIV-resistant mutations occur in a small number of people. By using CRISPR to introduce mutations into human stem cells, researchers can significantly enhance human resistance to AIDS in the future.

Another genetic editing trial in China will begin in July 2018, and scientists will try to use CRISPR to destroy the human papillomavirus (HPV) gene. This virus has been shown to cause cervical cancer tumor growth.

In a slightly different approach, scientists in North Carolina use CRISPR to design phage, which infects and replicates its own bacteria in bacteria to kill harmful bacteria. Phage have been used in clinical trials since the 1920s to treat bacterial infections. However, it is very difficult to harvest them from nature, because lack of understanding at the time leads to unpredictable results, and the growing market for antibiotics has made the use of phage unpopular. Even today, some researchers are concerned that a large amount of phage immersion may trigger an immune response or cause antibiotic-resistant bacteria to become resistant to phage.

Although human trials have not yet begun, researchers are optimistic about the use of CRISPR to design phage because they are a proven and safe way to treat bacterial infections. In fact, in a trial in 2017, researchers used CRISPR-modified phages to save the lives of mice infected with antibiotic-resistant bacteria.

3.CRISPR can resurrect extinct species

In February 2017, Harvard University geneticist George Church presented a surprising statement at the annual meeting of the American Association for the Advancement of Science (AAAS). He claims that his team can produce elephant-mammoth hybrid embryos within 2 years. Cherch hopes that the resurrection of the long-haired mammoth can control global warming. He said: "The mammoth can help the tundra thaw from the snow and let the cold air be released."

Church and his team hope to use CRISPR to combine the Asian elephants (the potentially endangered species that can be saved) with the genetic material of the mammoths. The latter sample was extracted from frozen mammoth DNA found in Siberia. By adding the mammoth genome to the Asian elephant, the final organism will have the common features of mammoths, such as long hair, which can be used as a thermal insulation material in cold climates. According to "New Scientist" magazine, the ultimate goal is to implant this hybrid embryo into the elephant and make it grow intact.

The prospects for this work are very gratifying, but many experts believe that the odd timetable is a bit too optimistic. Even if researchers develop mixed embryos, growing in artificial uterus will be another obstacle that needs to be overcome. Of course, the singular laboratory has the ability to use artificial uterus to develop mouse embryos. But this does not guarantee that we will witness the birth of the mammoth in the next few years.

4.CRISPR can create healthier new foods

CRISPR gene editing technology has proven to be very promising in agricultural research, and scientists from the Cold Spring Harbor Laboratory in New York use the tool to increase tomato yield. The lab developed a method to edit the genes that determine the size and branching structure of the tomato and ultimately determine the shape of the plant for more harvest. Lead researcher Professor Zachary Lippman of Cold Spring Harbor Laboratory said at the press conference: "Now, every feature can be controlled like a light switch. We can now use native DNA to enhance the natural offerings, which we believe can help Breaking production barriers."

In order to meet the needs of the world of hunger, high-yield crops are just the beginning, and scientists hope that CRISPR can also help GM crops get rid of stigma. In 2016, agricultural technology company DuPont Pioneer released a new variety of corn, which was technically not a genetically modified crop because researchers changed its genes.

The difference between GM crops and genetically edited crops is quite simple. Traditional GM crops pass traits or properties to future organisms by inserting foreign DNA sequences into the genome of the crop. Gene editing is more precise than this: it makes precise changes to genes at specific locations in the crop's own genome, often destroying certain genes or changing their position, and these are not related to the introduction of foreign DNA.

Although GM crops continue to be controversial among consumers, companies such as DuPont Pioneer hope that genetically modified foods will be better accepted. Genetically modified foods have been on the US market for decades, and scientists have not found any health risks, although the biggest supporters of GM crops admit that scientists still don't know all the long-term risks. The same is true for crops edited by CRISPR. Of course, scientists will continue to test and evaluate these crops to ensure that there are no unexpected side effects, but the initial work of this technology works very well. In the end, CRISPR editing crops may overwhelm the global market.

DuPont Pioneer hopes to bring its “waxy” genetically edited corn to the US market by 2020. The genetically edited mushroom has bypassed the US Department of Agriculture regulations because it does not contain foreign DNA from viruses or bacteria and became the first approved crop to edit the crop. Sweden has announced that it will classify and manage CRISPR editing genetic crops that are different from GM crops, but the European Commission has yet to decide its position.

5.CRISPR can eradicate the most dangerous pests on the planet

Gene editing technologies like CRISPR can directly fight infectious diseases, but some researchers have decided to slow the spread of the disease by eliminating transmission routes. Scientists at the University of California, Riverside have developed a mosquito that is particularly sensitive to changes in CRISPR, giving scientists unprecedented control over the characteristics that the creature passes to offspring. The result: yellow, three-eye, and wingless mosquitoes are created by altering the genes responsible for the development of the eyes, wings, and stratum corneum.

By interfering with target genes at multiple locations in the mosquito gene, the team is testing a "gene-driven" system to spread these inhibitory properties. Gene-driven is a way to ensure that genetic traits are inherited. By weakening the flight and vision of mosquitoes, the Riverside team hopes to greatly reduce its ability to spread dangerous infectious diseases in humans, such as dengue fever and yellow fever.

Other researchers have eliminated mosquitoes by interfering with the way mosquitoes multiply. Researchers at Imperial College London have used CRISPR to study the female reproductive patterns of malaria-carrying mosquitoes, which are genetically driven to affect the characteristics of female sterility, making them more susceptible to inheritance.

But interfering with the number of mosquitoes can have unpredictable consequences. Destroying a species, even a species that does not seem to have much ecological value, can undermine the careful balance of the ecosystem. This can have catastrophic consequences, such as destroying the food web or increasing the risk that diseases such as malaria may spread by different species.

The future of CRISPR

Current scientific advances show that CRISPR is not only an extremely versatile technology, it has also proven to be accurate and increasingly safe to use. But it still has a lot of room for improvement, and we are just beginning to see the full potential of genome editing tools like CRISPR-Cas9. While we use genetically edited food to meet human needs, eliminate genetic diseases, or resurrect extinct species, technical and ethical barriers still exist, but we still have to move in this direction.

Source: Bio 360

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