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Prodigies of the genetic cortapega

This report published in number 7 of the VERY Healthy has been awarded in the category of journalism printed in the prestigious awards given by Boehringer Ingelheim to journalism in medicine.

Gene editing

“One morning when waking up from an uneasy sleep, in a place in La Mancha whose name I do not want to remember, Gregorio Samsa found himself in bed transformed into a monstrous insect”.

This is how a novel created with a copy of the beginnings of The Ingenious Gentleman Don Quixote de la Mancha, by Cervantes, and La metamorfosis, by Franz Kafka. Almost as easily as we have composed a text, medicine already has tools to cut and combine fragments of the information contained in the DNA of any species.

The irruption of CRISPR / Cas9 has changed everything. This technique of genomic editing, erected by Science in the most important scientific advance of 2015 , not only allows modifying a text paragraph of the complete genome, but a single letter can be corrected – a nucleotide. CRISPR (short for palindromic repeats grouped and regularly interspersed) is based on a set of DNA sequences that bacteria use to defend against viruses. The strategy works as a molecular detective specialized in locating undesirable genes and is accompanied by proteins called Cas9, the scissors responsible for cutting the defective parts.

1. A therapy to cure root cancer

The revolution seems imminent especially because, besides e caz, it is a quick technique, non-toxic, cheap and quite easy to handle. Finding treatments for very common diseases that today have no cure is one of the promises that come with it; the experts in bioethics debate about their benefits and risks. Here we show some of the scientific hopes deposited in the genetic cutter.

Destroying all the tumor cells constitutes the holy grail of oncology and an almost impossible longing, because, if something characterizes them, it is that they are elusive and immortal. Australian scientists say they are on the verge of overturning the situation after finishing a lymphoma in their laboratory with the help of genetic editing.

As explained in Cell Reports, simply delete the MLC-1 gene, necessary for malignant cells to survive. There is no doubt that this tool will accelerate basic research, which could result in a rash of findings that help oncological diagnosis and treatment.

Without going any further, scientists from the University of Toronto, in Canada, used CRISPR / Cas9 to disconnect one by one 18,000 human genes – 90% of our DNA – and identify how many of them are necessary for cells to survive . The number of essentials amounted to 1,500. Some of them, they say, could contain the master key to curb cancer.

2. Goodbye to dengue and malaria

All the weapons of science have not prevented a frail mosquito from causing more than half a million people to die from malaria and 390 million from catching dengue every year, but the days of glory of the bug could be counted. .

Scientists from the Rockefeller University, in the USA. In the United States, they have modified the DNA of the female of Aedes aegypti, a mosquito that carries the microbes that cause yellow ewe, dengue and the ewe of chikungunya. “We thought it would be thorny to vary so many genes, but adjustments were enough to make the technique routine,” says Benjamin J. Matthews, co-author of the research. The result is exemplars that are unable to carry parasites and viruses from one animal to another. And without vectors that spread diseases, they disappear.

The same technique has been used at the University of California in the United States to insert anti-malaria antibody genes into mosquitoes of the genus Anopheles, and they have verified that the change is transmitted from one generation to another. And British scientists have chosen to use the technique to inactivate those that allow females to lay eggs. The result: the extinction of these diptera.

3. Pork organs for transplants

Xenotransplantation was already attempted in the 1990s. It was considered that the siological similarity that the pig keeps with man made it a suitable donor. And it was true, but the scientists had not counted on the unlucky tenants of the pig. When it was discovered that the endogenous porcine retrovirus could be transmitted to humans through hearts and other viscera, the alternative was parked. Every precaution seemed small, especially since it had just been discovered that HIV originated in African chimpanzees.

The reasons for taking them back came in 2015 when a team from Harvard University (USA) prevented the transmission of the virus by editing the pig’s genes. The researchers used the new molecular scissors to cut their DNA in 62 points. The clones of this animal with the inactivated retrovirus could form an army of donors of safe organs. “The potential impact is the number of lives that could be saved and overcome the abyss that separates the number of organs available for transplanting and that of people who desperately need one to survive,” said Donald Ingber, the bioengineer who co-authored the study published in Science .

4. Eliminate the AIDS virus

Once it reaches the organism, HIV inserts its DNA into the genome of the cells and remains silent until it decides to reactivate and completely destroy the defenses. Therefore, the optimal strategy would be to pay you in the same currency: cut and extract the fragments you have placed while the virus is latent to eliminate it before it is aggressive.

At the University of Massachusetts (USA) they used CRISPR / Cas9 to intervene in the sleeping HIV of the cells. “It’s the way to get to the root of the problem, the closest it has been to ending AIDS, ” say scientists from the Institute of Personalized Medicine at the University of Nevada, in the USA. In a job in the same line appeared in PLOS ONE . In the best case scenario, the therapy could reach patients in seven years and its use could be extended to other ailments, such as bird flu.

More controversial has been the attempt by Yong Fan and his colleagues at the Guangzhou Medical University in China to use the same procedure to immunize human embryos against the virus.

The twenty-six that they manipulated had defects and were not suitable for fertility treatments. They achieved their goal in four. Experts recommend that experiments of this kind be conducted in primates until more precision is achieved in the technology of the trimmer.

5. Without hereditary ailments

The cystic fibrosis or Down’s syndrome, among other ailments, may have their days numbered if genomic editing techniques reach the daily lives of doctors. “We are heading towards a more logical treatment that will allow us to say: ‘Your ailment is caused by this mutation, we are going to correct it and you will be cured,'” explained Basil Hubbard, a professor at the North American University of Alberta in Nature Methods.

Just as a text editor corrects a lack of spelling, scientists will correct the errors of unhealthy genes associated with these pathologies.

Before it is vital to make sure that the proteins that are injected to change the DNA only affect the target genes that you want to repair. Animal tests indicate that the CRISPR / Cas9 technique is specific, but safety must be ascertained before it is applied to patients. Hubbard opts for an option that emphasizes this feature, TALEN editing proteins (for its acronym in English of effector nucleases effector type of transcription).

“We can produce systems a hundred times more specific than those used until now,” he says.

From the University of Indiana and the Salk Institute of California propose to modify not the genes of the patients, but those of the previous generation, specifically those of the sperm and the ovules of the potential parents of individuals with hereditary disorders, and to correct the errors before fertilization.

A technically viable option that, for now, scientists discard. They argue that genetic modification in assisted reproduction is a line that should not be crossed.

6. End obesity

In the future we will have it easier to get rid of the kilos that we have if, as they announced last year from the Massachusetts Institute of Technology (MIT), genetic editing is used to put in 0 fat storage and activate permanently the burning of calories.

The proposal came after finding a metabolic pathway related to a genetic region called FTO that controls metabolism by prompting adipocytes to store or burn fat. Its DNA in turn in turn activates two genes, the IRX3 and the IRX5. These monitor thermogenesis, whereby the cells containing said region dissipate energy in the form of heat instead of keeping it.

If until now it was necessary to resort to exercise or to undergo a hypocaloric diet to initiate this process, as of this moment there would be an option to genetically stimulate the burning of reserves. It has been identified in individuals at risk that in the FTO area a thymine appears replaced by a cytosine.

An operation as simple as removing the first nucleotide and replacing it with the second one could interrupt the collection of lipids. Initial trials have already paid off. In human cell cultures in the laboratory, adipocytes were stopped from storing fat.

And in tests on living organisms, specifically in mice, Manolis Kellis and his colleagues found that genetic intervention causes a radical change in energy balance, which results in a reduction in body weight. What’s more, the rodents whose DNA was modified did not even get fat with a diet rich in lard, bacon and oils.

Will we be immune to junk food in the future? Will the love handles disappear from the human landscape? Everything points to the fact that the medical solution to obesity may be quite close.

7. End hunger

Almost eight hundred million people do not have enough food to reach an active and healthy life. And the worst thing is that, considering the growth of the population, the thing can only get worse.

One of the solutions is to develop crops that produce more fruits, cereals or vegetables per plant, that resist pests and drought, adapt better to climate change or provide an extra dose of nutrients.

“Genomics comes in step with plants that are the same as before with subtle changes, similar to those that occur naturally when mutations occur,” says Wendy Harwood, specialist at the John Innes Center (United Kingdom), which has already successfully tested CRIPSR / Cas9 technology in cabbages and barley.

8. Treat blindness

If a person explains to the doctor that she is blind from birth, her answer could be: “Do not worry, in a few minutes we activate your sight. I just have to give him an injection and he will start to detect the light. “Although, for the moment, this dialogue belongs to the field of science, in the future it could occur in any hospital in the world.

For the time being, scientists at Cedars Sinai Medical Center in California (USA) have already deleted a genetic mutation in rodents that causes retinitis pigmentosa, a degenerative eye disease that affects one in every 4,000 people and flows into the brain. No remedy in loss of vision. Specifically, they designed a CRISPR / Cas9 system to eliminate the wrong gene, which they injected into the bloodstream of rodents, as explained in the journal Molecular Therapy.

This prevented them from losing their sight. In cases of hereditary congenital blindness or caused by a genetic disease, this same technique could be returned to patients, say the authors of the study.

9. Avoid heart attacks

An injection that decreases the risk of heart attack by up to 90%. That is one of the miraculous promises that genomic techniques bring. “They are the main killers of the human being in their forties,” recalls Kiran Musunuru, of the Harvard Stem Cell Institute in the USA. UU

“If we could achieve a vaccine that reduces this risk by modifying the genome, we could consider this therapy as the solution for cardiovascular problems,” adds the professor. Above all, taking into account that a single injection also reduces cholesterol levels forever, the main enemy of blood vessels and the heart.

The idea came to him after it was discovered that 3% of people have a mutation in a liver gene related to this fat that makes their risk of heart attacks between 47% and 88% lower than the one of the average of the population.

“These people have had a biological lottery, and we thought that if we found a way to replicate it, we would be a panacea for cardiologists,” says Musunuru.

Said and done. With the help of CRISPR / Cas9, his team edited the mouse genome so that everyone could acquire this beneficial mutation. Three or four days after the molecules reached the liver; most copies of the gene in this organ had been modified.

At the same time, cholesterol levels were reduced by up to 40%, which in humans is equivalent to a 10% decrease in the incidence of heart attacks.

10. Relive mammoths and dinosaurs

What made us dream in Jurassic Park could cross the screen. The first species that could resuscitate are those that have been extinct relatively recently, such as the Tasmanian tiger, a carnivore that disappeared in the 20th century; or the bucardo of the Pyrenees, whose last specimen passed away. And, of course, the Pleistocene mammoths.

George Church, of the University of Harvard, in USA, advocates performing a sophisticated edition of the genes of an elephant until emulate the one of the mammoths. The condition to carry it out, both in these and in other extinct species, is that you have to know its complete genomic sequence to be able to rewrite it.

The thing does not end there. Maybe the fantasies you had as a child, when you dreamed of seeing dragons flying, become reality. In an article published in the American Journal of Bioethics, Hank T. Greely, director of the Stanford Center for Law and Bioscience, suggested that the new technique could be used to give life to beings, such as the dragon, which has so far they belonged to fantasy or mythology.

It would split from a large reptile and modify its DNA. “The method is cheap and simple, and could be used even outside the laboratory, escaping the control of legislators,” Greely says.

11. Save species from extinction

If Félix Rodríguez de la Fuente raised his head, he would remain attentive to the proposal of Josh Donlan, evolutionary biologist at Cornell University in the United States, which along with other US ecologists and biologists suggested in Nature that genetic editing tools have enormous potential for what they call assisted adaptation.

According to the researchers, it would be enough to rewrite some genes of endangered species, taking as reference other similar ones that have adapted well to the changes, to prevent them from disappearing. It is also considered to intervene on invasive populations that harm the environment, such as the lionfish that has colonized the Caribbean.


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