Antimatter trap, portrait of an ancient human, melanoma vaccine

Human DNA was edited directly inside the body for the first time

The biotech company Prime Medicine has begun a clinical trial of the method of prime editing of DNA — a technology that allows changing the sequence of nucleotides in DNA with high precision. For the first time this approach was applied to change genetic material directly in the human body.

The first participant of the study underwent treatment for Wilson's disease. This is a hereditary disease in which an excess of copper accumulates in the organism, affecting the liver and the nervous system. Today patients have to constantly take preparations helping to remove copper from the organism, and other medicines. Genetic editing directly inside the organism could theoretically provide a longer-term solution to the problem by correcting the defective gene.

Prime editing is a more complex method of changing DNA than the CRISPR–Cas9 technology. If CRISPR–Cas9 is most often used to switch off genes, then prime editing allows inserting, deleting and even rewriting sections of the genetic code. Earlier Prime Medicine had already applied prime editing to treat two patients with a rare immune disease. However then the specialists changed the DNA of stem cells outside the organism, and then returned them to the patients. The new approach presupposes editing the genetic material directly inside the body. The company from American Cambridge announced the start of the trials in October. The first results of the study are expected next year.

One of the main difficulties of such treatment is delivering the components of the genetic editor to the needed organ. For this small lipid particles are often used, similar to those used in some vaccines against COVID-19. They enclose the components of the editor inside and help deliver them into the cells. At the same time it is necessary to achieve that the particles act on the needed organs and, if possible, do not affect other tissues.

There is also another problem: when DNA is edited outside the organism, the researchers can check the result before the changed cells are returned to the patient. When editing directly inside the body there is no such possibility.

Despite the difficulties, interest in this approach is growing. Treatment directly in the organism potentially may turn out to be faster and cheaper than individual methods, in which the cells of each patient have to be extracted, changed in the laboratory and introduced back.

So far no genetic therapy presupposing editing of DNA directly inside the organism has received approval for use. It is expected that at the beginning of 2027 the US Food and Drug Administration will deliver a decision on the therapy based on CRISPR-Cas9, which is introduced directly into the organism for the treatment of hereditary angioedema.

The begun trial of prime editing became another step toward the development of such an approach. Clinical trials of other genetic methods of editing DNA inside the organism (in vivo) are underway.

A trap for antimatter

Physicists from Northwestern University (Evanston, USA) held a single particle of antimatter in a magnetic field and cooled it to the minimum possible energy state. This experiment will allow measuring the magnetic properties of the positron with unprecedented precision and suggesting what distinguishes matter from antimatter. The answer to the latter question is one of the main mysteries of the physics of the Universe.

According to the Standard Model — the modern theory describing elementary particles and the interactions between them — during the Big Bang approximately equal amounts of matter and antimatter should have formed. Their particles have the same mass but differ in some properties, for example electric charge. For example, the positron is the complete twin of the electron, only with a positive charge instead of a negative one. Therefore the electron is an element of matter, but the positron is antimatter. Upon meeting they annihilate, turning into energy.

For the experiment the scientists used positrons arising during radioactive decay. First the fast particles were slowed, forcing them to collide with atoms in a tungsten crystal. Most of the positrons annihilated, but the slowest of the survivors fell into the trap, which the researchers “assembled” from electric and magnetic fields. In the trap a single positron was fixed. In it a temperature of only 0.3°C above absolute zero was maintained and an almost ideal vacuum was created. This allowed the particle of antimatter to remain “on a leash” for several months.

When the positron reached the minimum possible energy state, the scientists acted on it with microwave radiation, causing quantum jumps — sharp transitions between states of spiral motion in the magnetic field. Now the next stage of the research is underway: measuring the frequencies at which these transitions occur. This will allow determining the magnetic moment of the positron — a characteristic connected with its behavior in a magnetic field.

Analogous measurements for the electron this same team conducted in 2023. Now it will be possible to compare the results and check whether the magnetic moments of the particle and antiparticle are exact opposites. If yes, this will once again confirm the Standard Model. If discrepancies are found — a number of fundamental ideas at its base will have to be reconsidered. And this is not the first time for scientists. The Standard Model, of course, possesses high precision of predictions, but something still does not fit into it. For example, it cannot explain the nature of dark matter.

A personalized mRNA vaccine lowered the risk of melanoma returning

A personalized vaccine against melanoma based on messenger RNA (mRNA) in combination with immunotherapy lowered the risk of cancer recurrence or death by 42% within two years after treatment. This was shown by the third phase of an international clinical trial under the leadership of Australian scientists, in which 1,137 patients participated.

The results of the study were presented on October 23. The trial involved patients with melanoma — a dangerous form of skin cancer — whose tumor had been surgically removed but who retained a high risk of recurrence. All participants for 12 months received the immunotherapeutic preparation pembrolizumab. Part of the patients additionally received an individual mRNA vaccine called intismeran.

Two years after treatment 82% of the patients receiving both preparations remained alive without recurrence. In the group receiving only pembrolizumab this indicator was 70%.

Intismeran is being developed by the companies Moderna and Merck. Unlike ordinary vaccines intended for the prevention of infections, this therapy is aimed at an already arisen oncological disease and the peculiarities of the tumor of a specific person.

To create the preparation the specialists analyze the genetic changes in the patient's tumor and compare them with healthy cells. Then they select up to 34 characteristic mutations and use the obtained data to develop an individual mRNA vaccine. It helps the immune system recognize proteins specific to the tumor — the so-called neoantigens — and attack the cells that produce them. In combination with pembrolizumab the vaccine must strengthen the antitumor immune response and lower the probability of the disease returning.

The study took place at 157 sites around the world. Its results have been accepted for publication in The New England Journal of Medicine and presented at the annual congress of the European Society for Medical Oncology in Madrid.

But it is still far from wide application. First, despite the encouraging results, the treatment does not suit all patients. According to the researchers, part of the people do not respond to the vaccine, and cancer cells are capable of adapting to the therapy and avoiding the impact of the immune system. Second, there is so far insufficient data to determine whether the combination of preparations improves long-term survival. Third, it must still be found out how effective the approach is in patients with tumors that are still present in the organism, and in those whom pembrolizumab does not help. Not to mention that the creation of a personalized vaccine is monstrously expensive and certainly will not be available to every patient with melanoma.

Personalized vaccines have not yet been adopted as the standard of treatment for melanoma. For this additional research and approval by regulatory bodies will be required, which may take several years.

The Denisovans were “given a face” for the first time

Scientists from the Chinese Academy of Sciences for the first time attempted to describe the appearance of the Denisovans — a side branch of human evolution. Everything says that they did not especially differ from the Neanderthals: a low sloping forehead, a massive brow ridge curved backward, almost rectangular eye sockets, flat cheekbones and a moderately protruding bridge of the nose — approximately thus looked the ancient people who lived in the east of Eurasia hundreds of thousands of years ago. From other species of ancient people they were separately distinguished by a flattened, elongated shape of the skull and an almost vertical plate-like bone in its rear part. Such conclusions the researchers made by studying in detail the fossilized fragments of the skull, teeth and jaws found in the north of present-day China.

The Denisovans were first described in 2010. The first material that told us about them was a finger phalanx in the Denisova Cave in Siberia. From it DNA was successfully sequenced. By it they understood that these were neither us nor the Neanderthals. Then in various corners of Asia other remains of our ancient “cousins” were found — they determined that these were them by the analysis of ancient proteins (they are preserved better than DNA). It seems that the Denisovans 300 thousand — 45 thousand years ago inhabited vast territories — from the northeast of East Asia and the Qinghai-Tibet Plateau to the southwestern and southeastern regions of China and part of Southeast Asia.

Until now there were no important criteria by which scientists could clearly identify that before them were precisely the remains of Denisovans. An important find at one time became the almost complete skull that was found near Harbin. It helped compose a general idea of the appearance of the Denisovans.

But an even clearer idea was given this week, when a new article was published — based on the remains of Denisovans found in the 1970s in Xujiayao. These bones are 130 thousand years old. Anthropologists from China have finally identified the morphological features of the skull, jaw and teeth characteristic of this species of people. Now there is a basis for the first system of identifying Denisovans by morphological characteristics — 16 years after their discovery.

Blood cells were rejuvenated

Researchers from the University of Bonn (Germany) have devised how to turn immature human blood cells into stem cells of the nervous system and along the way substantially rejuvenate them. It was possible to completely skip the intermediate stage (when first a universal stem cell is obtained, and then it is differentiated). But the main thing — during such a transformation it was possible to substantially reduce the epigenetic age of the cell. The “rejuvenating” changes occurred gradually and continued for about 50 days.

The researchers studied the cells of donors aged from birth to 101 years. With the help of two reprogramming factors — the proteins SOX2 and cMYC — they transformed the blood cells into induced stem cells of the nervous system. Such precursor cells are capable of giving rise to various types of cells, including neurons. To assess their “age” changes, the researchers used epigenetic clocks — a method that determines the biological age of cells by the peculiarities of DNA methylation. This process influences the activity of genes without changing the very sequence of the genetic code.

It turned out that in the cells obtained from elderly donors the epigenetic age substantially decreased. At the early stages of cultivation it amounted on average to about 13% of the donor's age, and in later cell cultures it dropped to about 5%. At the same time the rejuvenation did not occur instantly. The main part of the age-related epigenetic changes disappeared in about 50 days. The scientists also discovered that as reprogramming proceeded the cells obtained from young and elderly people became ever more similar in gene activity.

At the same time the reduction of epigenetic age did not depend directly on the active division of cells. It continued even when the multiplication of cells was artificially slowed. Besides, the process was preserved during the transformation of induced stem cells into neurons. The authors consider that slow reprogramming gives the possibility to study the mechanisms of cellular aging and to find out which processes allow cells to return to a younger state.

However these results do not mean that the scientists have found a way to rejuvenate the brain or the whole human organism. The research was conducted on cells in the laboratory, and the epigenetic age reflects only separate sides of aging and does not give a full assessment of the functional state of cells.

In the future this model may help study the mechanisms of aging of the nervous system and develop approaches to studying age-related neurodegenerative diseases, including Alzheimer's disease. But it is still far from the application of such methods for treating people.