CRISPR for dummies
A short guide to the main biotechnology
Sergey Kolenov, Hi-tech+
CRISPR is one of the most promising technologies of recent years, and its role will only grow in the coming years. However, not everyone understands exactly how gene editing works. Vox has presented a simple reference guide that will help even a person far from biology to understand CRISPR.
In short, CRISPR – more precisely, CRISPR/Cas9 – is a powerful genome editing tool. It is based on an element of the bacterial defense system, which biologists have adapted to make changes to the DNA of plants, animals and even humans. The technology allows you to make corrections in just a few days, not weeks or months. Never before has humanity had such an accurate tool for manipulating genes.
The history of CRISPR began in 1987, when Japanese scientists who studied Escherichia coli found in its DNA has unusual repeating sequences. Their biological significance could not be found out, but soon similar fragments were found in the genome of other bacteria and archaea. The sequences are called CRISPR – short palindromic repeats, regularly arranged in groups (Clustered Regular Interspaced Short Palindromic Repeats).
Their function remained a mystery until 2007, when experts on the bacterium Streptococcus, which is used for the preparation of fermented milk products, determined that these fragments are part of the bacterial immune system.
The fact is that bacteria must constantly repel the attacks of viruses – their natural enemies. To do this, they produce special enzymes. Every time a bacterium manages to kill a virus, it cuts up the remnants of its genetic material and stores them inside CRISPR sequences. This information is then used in case of a new virus attack. When attacked, the bacterium produces Cas9 proteins that carry a fragment of the virus' genetic material. If this site and the DNA of the attacking virus match, Cas9 cuts the genetic material of the latter and neutralizes the threat.
For some time, this discovery was interesting only to microbiologists. However, everything changed in 2011, when biologists Jennifer Doudna and Emmanuel Charpentier decided to study the mechanism of CRISPR more precisely. They found that the Cas9 protein can be tricked by giving it artificial RNA. A protein carrying such an RNA will look for genetic fragments that match what it carries on itself. Having found a match with someone else's DNA, he will begin to grind it, regardless of whether it belongs to a virus, plant or animal. As noted in a 2012 article by Dudna and Charpentier, this mechanism can be used to cut any genome in the right place.
In February 2013, it was proved that CRISPR/Cas9 can be used to edit DNA in mouse and human cell cultures. Moreover. it turned out that the technology allows not only to remove unnecessary genes, but also to insert others in their place. To do this, it is enough to add enzymes that restore DNA.
Scientists quickly realized the huge prospects of CRISPR. If in 2011 only 100 works about her were published, by 2017 this figure reached more than 14,000.
Among other things, they described analogues of Cas9 proteins. For example, Cas13 can edit not DNA, but RNA.
The idea of gene modification is not new, and its various methods have been around for many years. However, CRISPR surpasses all technologies known so far due to its availability and accuracy. Editing a single gene will cost only $75 and will take several hours. And, importantly, the technology works with any organism on Earth.
There are almost an infinite number of potential applications of the technology. First, CRISPR allows scientists to figure out the function of various genes. It is enough to simply cut the gene under study from the DNA and see which body functions were affected. However, the public is much more interested in practical applications. They can be divided into several points:
1) Changes in agriculture
CRISPR allows you to make crops more nutritious, more tasty and resistant to heat and stress. You can also give plants other properties: for example, cut out the allergen gene from peanuts, and introduce resistance to a deadly fungus into bananas. The technology can also be used to edit the genome of domestic animals – for example, cows.
2) The fight against hereditary diseases
Scientists intend to use CRISPR to cut out mutations from the human genome responsible for a number of diseases, for example, sickle cell anemia. The technology will also allow cutting out the genes of Huntington's chorea or BRCA-1 and 2 mutations associated with breast and ovarian cancer. Theoretically, a CRISPR attack can even stop the development of HIV.
However, specialists will have to make sure that the technique is safe before it can be used in hospitals. Cas9 enzymes sometimes make mistakes and edit DNA in unexpected places, which can cause serious health consequences.
3) New antibiotics and antiviral drugs
Bacteria develop resistance to antibiotics, and it is expensive and difficult to develop new ones. CRISPR technology makes it possible to destroy certain types of bacteria with high accuracy, although a specific technique has yet to be developed. A number of researchers are also working on CRISPR systems aimed at viruses.
4) Genetic drive
With CRISPR, you can change not just the genome of an individual animal and plant, but also the gene pool of an entire species. This concept is known as "genetic drive". Usually, any organism passes on half of its genes to offspring. However, the use of CRISPR makes it possible to increase the probability of gene transmission by inheritance to almost 100%. This will allow the desired trait to spread quickly throughout the population.
Using this technology, it is possible, for example, to modify mosquitoes so that only females are born in their population. After some time, the population will disappear.
In a more gentle version, it is possible to make mosquitoes resistant to infection with malaria plasmodium. They will not be able to transmit the parasite to humans, and malaria will be put to an end. However, in order to implement such projects, it is necessary to overcome the doubts of skeptics who protest against such a large-scale invasion of nature.
5) Creating "designer babies"
This item attracts the most public attention. However, according to scientists, so far our technological capabilities do not allow us to create children with the specified qualities. For example, thousands of genes are responsible for the level of intelligence, and it is not yet possible to correct them all. Perhaps in the future the technology will reach the right level, but for now there is nothing to worry about.
Not all scientists consider CRISPR to be a safe technology. For example, according to recent studies, gene editing can cause extensive non-targeted mutations. The authors of another paper note that CRISPR is wrong in 15% of cases.
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