Annual Review – Advances in HIV Prevention and Autoimmune Diseases

The drug Lenacapavir is the next, but by no means the last step in the fight against AIDS, writes Holden Thorp, editor-in-chief of the journal “Science,” in his homage to the scientific breakthrough of 2024. Every year, the renowned journal chooses a research result »Breakthrough of the Year«.

The new drug is intended to offer long-term protection against HIV infections and has recently proven this in a study among girls and young women in South Africa and Uganda with an effectiveness of an astonishing 100 percent. In another study involving people of different genders on several continents, it showed an effectiveness of 99.9 percent.

Lenacapavir is not yet the long-awaited vaccination against HIV, but rather a form of pre-exposure prophylaxis (PrEP) – these are medications that have so far been taken in tablet form and protect against infection, for example during sex. The use of PrEP is particularly widespread in gay communities – but only where they have access to the drug. If people are stigmatized or criminalized because of their sexual orientation, they also have fewer opportunities to optimally protect themselves.

Long-term HIV protection could reduce the number of new infections

Lenacapavir now has the advantage over daily tablets in that it only needs to be injected once every six months. As in the successful effectiveness study, a target group for PrEP could be young women in regions where HIV and AIDS are widespread. With the injection, women could protect themselves discreetly without being suspected of taking AIDS medication by those around them. The biannual injection could help bring the goal of the United Nations Joint HIV/AIDS Program (UNAIDS) of reducing new infections per year to below 200,000 by 2030 within reach, says “Science”.

Of course, the prerequisite for this is that poor countries and emerging economies can afford the widespread use of PrEP. The pharmaceutical company Gilead has already signed a contract with six generic drug manufacturers to produce lenacapavir cheaply for 120 poor countries, the science magazine reports. However, there are currently no preferential conditions for middle-income countries like Brazil – with a high number of HIV-infected people.

The new form of PrEP is being celebrated not only because it could make HIV prevention easier for many people, but also because it uses a new mechanism of action. It attaches to the capsid, the protein coat that surrounds the virus’s genome. This is hardened by the drug, which prevents it from penetrating the nucleus of host cells. In addition, the reproduction of the virus is also disrupted. Both together apparently resulted in 100 percent effectiveness.

With modified immune cells against autoimmune diseases

In addition to the breakthrough of the year, “Science” names a whole series of runners-up. Among these, another medical innovation, the treatment of autoimmune diseases with Car-T cells. Car T cell therapy has been used against leukemia for 15 years, but it is often associated with serious side effects. T cells, which play an important role in the body’s immune defense, are obtained from the patient’s blood. They are then propagated in the laboratory and modified so that they can better recognize and fight cancer cells in the body. As chimeric antigen receptor T cells (Car-T cells), they are finally given back to the respective patients.

This year, German research teams reported that they had successfully treated the autoimmune disease lupus in eight cases using Car-T cells. Patients with other autoimmune diseases who had also been treated with Car-T cells sometimes still had symptoms, but were then able to stop taking their immunosuppressants.

Chinese rheumatologist Huji Xu from the Naval Medical University in Shanghai also reported success in treating autoimmune diseases with Car-T cells. The three patients he treated showed improvement within a few days. The special feature of Xu’s treatment was that he did not use modified cells from the patients themselves, but rather cells from donors. These were modified by another scientific team led by Du Bing from East China Normal University in Shanghai using the Crispr/Cas9 gene scissors so that they should not trigger an immune reaction in the recipients.

The renowned specialist journal was chosen for its courageous approach »Nature« Hu among the ten people who shaped science in 2024. After the first report of success, Hu treated 24 other people with the same method. As with all new medical treatments, it does not just require the courage of the doctor, but certainly also that of the patients who undergo such experimental therapies.

Pesticides without conventional agricultural chemicals

Genetic engineering interventions are not only celebrated by the leading scientific journals in the field of human medicine: “Science” also has pesticides with new, and according to the manufacturer, particularly targeted mechanisms of action on its list of outstanding scientific achievements.

These are RNA-based pesticides that target exactly one gene of the pest they are intended to combat. The company Green Light Biosciences in the USA has developed a remedy against the Colorado potato beetle, of which, according to the company, only 9.9 grams need to be applied per hectare, “as much as a spoonful of sugar spread over a football field.” The agent that is sprayed on the leaves of the potato plant is based on RNA interference (RNAi). In this inherently natural mechanism, RNA snippets block the expression of certain genes. In the new pesticide “Calantha”, which was approved by the US Environmental Protection Agency (EPA) this year, RNAi causes the death of the Colorado potato beetle larvae when they eat the treated leaves. The agent blocks the expression of a vital protein in insects.

In 2007 it was discovered that double-stranded RNA can penetrate the intestinal lining of insects. Since then, researchers have placed great hopes on RNAi as a method for combating various insect pests. A genetically modified type of corn has been on the market since 2023, which itself produces RNA that is deadly for the corn rootworm. Green Light Biosciences has applied for approval from the EPA for another RNAi-based agent: “Vadescana” is intended to protect honey bees from infestation with Varroa mites. According to the company, the RNA pesticides break down quickly and do not pose a burden on soil or water.

But if RNA pesticides are used on a larger scale, a well-known problem will arise again: Insects often become unimpressed by the poisons that are intended to combat them within a short period of time. In laboratory tests, both the Colorado potato beetle and the corn rootworm have already developed resistance to the RNA, which was supposed to kill them when it was given in high doses.

RNA pesticides could nevertheless develop into an important new market segment for agricultural chemical manufacturers. In Europe in particular, RNA pesticides could be more effective than plants that produce their own insect-damaging RNA. While such plants are considered genetically modified, this does not apply to spraying products.

“The drug Lenacapavir is the next, but by no means the last step in the fight against AIDS.”

Holden Thorp »Science«

The history of multicellular organisms must be rewritten

Not all of the year’s scientific breakthroughs necessarily have a useful application for people; some simply contain astonishing gains in knowledge.

A discovery of tiny fossils from China could lead to the need to correct the origins of life on Earth. The algae-like fossil Quingshania magnifica was found and first described in 1989. And although it came from a 1.6 billion-year-old rock formation in northern China, the study that described the fossil received no particular attention at the time.

Only in a paper published in “Science” in January 2024 Study The formation was proven to be full of fossils of this species – 279 were collected in total. They consisted of strands of up to 20 cells. Some even had spores, suggesting a reproductive system. Further investigations showed that they were eukaryotes, i.e. living beings like all plants, animals and fungi found today, whose cells contain a cell nucleus.

In contrast, there are prokaryotes, such as bacteria, which do not pack their genetic information into a cell nucleus. According to previous assumptions, 1.6 billion years ago multicellular prokaryotes would have been found at best, but not eukaryotes. According to current evolutionary history, eukaryotes only began to form simple multicellular structures about a billion years ago.

The theory that eukaryotes became multicellular 600 million years earlier is also supported by other finds of algae-like fossils from similarly old rock formations in India, Canada and Australia. Everything indicates that eukaryotes became multicellular 1.6 billion years ago. In order to develop truly complex organisms, they took a little more time than previously thought.