14 November 2014

A new breakthrough in genetic engineering

What are the prospects for gene therapy and the latest methods of genome editing?

Post -scienceDoctor of Physical and Mathematical Sciences, Professor, Faculty of Biomedical Engineering, Boston University (USA)

Maxim Frank-Kamenetsky talks about the revolution in genetic engineering, gene therapy and medical tasks of genome editing.

Genome editing based on the CRISPR/Cas9 system is a completely new technology that emerged only last year. The first publication about it appeared in early 2013, and during this time hundreds of articles with examples of using this technique have already been published. Two other genome editing approaches are being developed in parallel: ZFNs (Zinc-finger nucleases) and TALENs (Transcription activator-like effector nucleases). However, they are much more time-consuming, less elegant and more expensive.

Over the past 25 years, scientists have gradually discovered and investigated a completely new mechanism of immunity in bacteria, which has been called CRISPR. The first work that eventually led to this outstanding discovery was published in 1987. However, this article went completely unnoticed at that moment. The discovery of CRISPR was a significant breakthrough when one of the variants of this system was adapted to the cells of higher organisms.

The mechanism of using the CRISPR/Cas system is that the DNA is cut and a double-strand break is inserted into it. Moreover, the DNA molecule is cut in a very specific place, which is programmed by the small RNA molecule that is injected into the cell. Today, examples of using this method exist for almost all types of organisms, and it is important that, unlike traditional genetic engineering, the methods of which have been used for several decades and which arose after the discovery of restriction enzymes capable of recognizing certain sequences in DNA, making a double-strand break in it, CRISPR/Cas9 allows you to do these genetic engineering manipulations in a living cell.

In traditional genetic engineering, DNA cutting and crosslinking are carried out separately in vitro, in vitro, and after that the DNA is injected into the cell. This led at one time to the revolution that marked the beginning of biotechnology.

The peculiarity of the new breakthrough is that the same manipulations are carried out in a living cell, in which the DNA molecule is cut and the site is inserted from the outside into this cell. The genetic material of a living cell is changed without manipulation on the isolated DNA.

This opens up completely new perspectives and allows us to talk about real gene therapy, which is no longer a futurological speculation, but reality. Simultaneously with the application of CRISPR to genome manipulation, the methods of ZFNs and TALENs, which up to this point were mainly developed in the biotechnology industry, were also brought to specific applications. Now a whole arsenal of methods has been developed, with the help of which genetic therapy of diseases is already being carried out in animals (mice and even monkeys).

What is genetic therapy? For example, you have a bad gene and you want to replace it with a good one. You introduce this good gene in the form of DNA into a cell, and a CRISPR system is introduced into the same cell, which cuts DNA, and a short RNA molecule that directs this cutting mechanism, these "scissors" to the right place in the genome. These "scissors" cut out a bad gene, and a good one is built in its place. Such gene therapy is already being carried out on live animals, and they are recovering.

The next stage is to bring these methods to use in medicine. The timing of these tasks depends on a lot of circumstances. But judging by the way the start was taken, examples of some specific applications on humans will appear within a few years or even months. First of all, these methods will be used to treat lethal diseases from which a person should die very soon. In the near future, genetic therapy will depend on the severity of the disease. This may not be as common as plastic surgery. We interfere with the work of the cell, and there will always be side effects. The cell can turn into a cancerous one.

The CRISPR/Cas system is used not only for the treatment of genetic diseases. This gives a completely new impetus in synthetic and systems biology, in the field where people modify the genome to make the cell do something new, which it did not know how to do before.

Another medical application of CRISPR is the creation of animal models for medical purposes. This is the creation of animal models that are endowed with properties similar to those of sick people. With the help of animal models, it is possible to study the disease and develop ways to treat it. It is much easier to work with animals than with people: a large number of prohibitions are removed. The preparation of such animal models with a modified genome before the methods using CRISPR were developed was a very time-consuming, expensive task that required the participation of highly qualified specialists. Now this process has become much easier, which is of great importance for modern medicine.

Portal "Eternal youth" http://vechnayamolodost.ru14.11.2014

Found a typo? Select it and press ctrl + enter Print version