02 December 2015

Genomic engineering

David Sinclair, Postnauka

One of the most interesting people in the world was Jeanne calment. She lived to 122 years, setting a record among centenarians. It is no longer with us, but she's lived a great life and was an energetic woman with a great sense of humor.

I heard an amazing story of how a young French reporter in her birthday interviewed and saying goodbye, he asked: "Perhaps, we will see you next year?", and Kalman said, "Why not, you look quite healthy" – that was her sense of humor.

She joked: "I only Have one wrinkle and I'm sitting on it". Kalman enjoyed life. I think she quit Smoking in only 90 and overall a little in what was limiting myself. Nice if everyone could live like her.

Latest achievements of science: a revolution in genomics and the ability to sequence thousands, and soon millions of human genomes allow us to study people like it; a lot of the samples taken from the centenarians are stored in laboratories around the world. We can analyze these genomes, compared with the genomes of ordinary people and ask ourselves: what is the difference in the genes, is there something that makes them special?

We already know several genes that may be associated with the families of centenarians. People from such families often live to be a hundred, and their descendants. But the most important will happen very soon: sequencing the genomes of thousands of people will help you to figure out what genes are and help them to live longer, and we – the ordinary period. To know that in itself is very interesting, but how to use this information?

One of the directions is the development of new drugs, dietary supplements, which, for example, could make the pathways of people like me work just the same as that of Jeanne calment. However, the development of new drugs requires a lot of time and there is no guarantee of success.

Now I will talk about the approach, which, I think, has all the chances of success and which could be an interesting way to extend the life of ordinary people, like me, to the level of families of centenarians. I'm talking about genome engineering.

It is a rapidly evolving technology that offers a number of methods, not limited to laboratory experiments. Everything goes to the fact that we will be able to edit our body cells to take stem cells, modify them and return to the place. And this is a radically new direction in medicine and biology.

You imagine that can give us the ability to edit the human germ cells. Sex cells determine what will our offspring.

Perhaps not many years will pass before we will be able to work with human cells – from the sex cells. We can take the germ cells of men and grow their culture in the laboratory. Also recently, when starting from 2012, we can take stem cells from women to raise their eggs. In my Harvard lab, we are engaged in, and these cells we can cultivate millions.

What it gives us? In fact, it allows us to change the human genome. One of the very interesting practical applications – the ability to cure genetic diseases. I think in the near future we will be able to adjust some things. For example, imagine a family with Huntington's disease is a dominant genetic neurodegenerative disease. What we can do is to take stem cells from the ovaries of women with the disease and to raise millions of eggs. Then we can use the latest technology to edit the genome. This allows with high accuracy to change single DNA bases or even entire sequence. You can even change the whole malicious stretches of DNA. This edit will make possible the birth of healthy offspring of parents with genetic diseases. And I think in such cases, parents will be able to go to the right people and say: "we Have such a list of issues that we don't want to pass on to their children," and we will be able to help them.

In fact, now we're one small step away from opportunities to change any gene in our posterity. Of course, there is some ethical problems that we cannot ignore. However, I would like to focus on what I think we can achieve: we can work with the genes responsible for susceptibility to health and longevity. We can change these genes, helping people to live longer and be healthier, in addition to have resistance to known diseases.

When we start to do it and when society is ready for it – is unclear. But I believe that if, one day, people will gather to explore other planets (and it seems to me that for the survival of our species to do it is almost necessary), this technology will be the key that will help us to survive a thousand-year journey to another solar system.

One of the remarkable features of this method is that we can clone stem cells many times – in fact, almost indefinitely. We can obtain an infinite number of copies of a single donor cells, to select and sequence the clones to be sure that there will be a mutation that introduces malignant changes, and back to implant cells that we want. Thus, we can guarantee that of the edited cells will posterity – that's what parents want.

Returning to the issue of ethics and security: I think the discussion of both topics is very important, but our main priority is safety. We have to minimize all possible risks.

One of the potential problems is that if we do these studies, in the process discover hundreds of genes that affect life expectancy. So, maybe, we can not with certainty to say. If so, then we are faced with great difficulties when you try to edit such material. But I still hope that genes positively influencing the life expectancy is not so much. For example, we know that there are certain genetic characteristics of the families, long-lived, affecting insulin receptor (receptor, which is activated by insulin) have significant positive effect on health and life expectancy. So we still have a lot to learn, we'll analyze thousands of genomes of centenarians and see what distinguishes them. Then we do the research and determine how many and which genes you want to change the person that he lived longer. It is, as I said, it may be necessary for us if we want to live on other planets.

I will give an example of how this technology can be applied in the near time. Imagine a family with an inherited mutation in the BRCA1 gene is a so – called gene of breast cancer, in the case of mutation of women from a family and their descendants are likely to develop cancer of the breast, this is a serious problem in such families. What we do in our lab? We can take stem cells from the ovaries of a woman with breast cancer and a mutation in the BRCA1 gene and grow them in the laboratory. In the end, we will receive a harvest in the form of thousands or even millions of such cells. Each daughter cell will contain a mutation inherited from the donor cells.

The next step is to edit the genome using new enzymes and RNA-guided proteins that can specifically change a single base in the genome of cells. We want to achieve correction of this mutation on the BRCA1 gene is wild-type, normal, and we have already received some encouraging results. For example, we were able to do that, we have successfully corrected the mutation, and now we have a a healthy stem cell. I think the future is preparing for us an opportunity to find ways to develop it into an egg, suitable for fertilization, which can be done with the help of sperm in vitro. Methods for this now being developed in many laboratories, with which we cooperate. Another solution would be to take the corrected stem cells and place them back in the female ovaries to Mature in her body. We think that this will work, since you already have the results of studies carried out on mice, and there is some evidence of experiments on monkeys, showing that it really works, what are stem cells, placed in the ovaries, give healthy offspring.

Thus, irrespective of, they ripen in vivo or in vitro, edited stem cells can produce healthy offspring. As a result, parents who are afraid of passing on a genetic disease to their children will no longer be able to worry about it. We will be able to assure them that we will correct this mistake so that not only the descendants themselves, but also subsequent generations will not inherit this disease.

About the author:
David Sinclair – Professor, Department of Genetics, Harvard Medical School; Co-joint Professor, Department of Physiology and Pharmacology, University of New South Wales; Co-Director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging and a Senior Scholar of the Ellison Medical Foundation

Portal "Eternal youth" http://vechnayamolodost.ru
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