May 16, 2021

Genetic Crispr: The genetic chain reaction reaches mammals | Science

Genetic Crispr: The genetic chain reaction reaches mammals | Science



In all our cells there are two copies of each gene and each one has, in principle, a 50% chance of moving on to the next generation. However, there are genes that skip that norm and start transmitting more frequently. It is believed that this phenomenon, the genetic drive, known as gene drive in English, is important for the appearance of new species, but the development of new technologies makes it possible to manipulate it to introduce genetic changes that in a few generations modify the genome of a whole population of animals.

This has been achieved with the mosquitos that transmit malaria. Last year, a team of scientists from the Imperial College of London (United Kingdom) annihilated a population of these insects introducing in the group a genetic mutation that made females sterile. With the Crispr editing technique, they changed a key gene in 12% of a population of 600 insects and started a chain reaction. In one year, the mutation spread and between seven and eleven generations later there was no live mosquito left in a group that, if it had reproduced normally, would reach 20 million.

The effectiveness of the technique is still small, but it can help to create better mice to study diseases

This week, a team from the University of California at San Diego led by Kimberly Cooper explains in the magazine Nature that this technique, which would make it possible to eradicate populations of mosquitoes that transmit diseases such as malaria, dengue or zika, can also be applied to mammals, although with more limitations.

In their experiments, the researchers played with a genetic variant that produces albino mice. To insert it, they designed males and females with different components of the Crispr / Cas9 genetic cut-off system with which they selected the piece of DNA to be cut and the sequence with which it was to be replaced. With this technique they were able to increase the natural rate of transmission of the mutation that produced white mice of 50% up to 72%, but that success was only achieved in the females. For the changes in the genome to pass to the next generation, it is necessary that the system be activated at a specific moment in the development of the embryo and how the rhythms are different in males and females in one sex worked and in the other, no.

The results confirm that this genetic chain reaction can be applied to mammals, but also indicate that it is less effective than in insects. Cooper explains that to consider applying the genetic impulse to the eradication of rodent pests, such as those that threaten the native fauna of many islands of the planet, they still have to learn a lot about when to apply the technique and how to avoid the resistances offered by the systems of security of an organism before the attempt to manipulate its genome.

A scientist who proposed using this technique to eradicate invasive species now considers it very risky

"I think both optimism about the possibilities of [esta técnica] to reduce populations of invasive rodents as concerns [por sus riesgos] They are premature, "said Cooper. "There may be unforeseen consequences, but I also think that scientists are working hard to anticipate them and develop methods to mitigate risks," he explains. An example of this risk would be that a genetic impulse spread outside the geographical area in which it is wanted to apply, an island, for example, and provoke an ecological hecatomb. However, according to Cooper, "scientists are thinking of mechanisms to self-limit the genetic impulses to reverse such a result".

One of the applications that seems closer and also more secure is the creation of animal models with a series of specific mutations that mimic those that produce certain human diseases. Michael Wiles, director of technical evaluation and development of the Jackson Laboratory in Bar Harbor (USA), one of the world's leading producers of modified mice for research, commented in Science Magazine that this method can be very useful. "I am receiving orders to make mice with six genetic modifications, and the breeding time is phenomenal," he explained. With a genetic impulse like this, what now requires a work of five years, could be done in one.

On the pessimistic side of the meaning of this technology is Kevin Esvelt, of Harvard University, one of the first who thought that this genetic impulse could be used to control pests. Last year, he published a mathematical model in which he observed that these genetically modified organisms have a great risk of spreading out of the environment from which they want to eradicate. In an interview with the New York Times, he acknowledged that defending the idea of ​​using this technology as a way to reestablish ecological balances had been "a shameful mistake"

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