Synthetic biologists have created a slow-growing version of the coronavirus to give as a vaccine


sabin needle

BELAWAR CO KOLEKTN

In the 1950s, Albert Sabin was looking for a better polio vaccine. For this purpose, his laboratory infected the brains of mice, chimpanzees, and monkeys with the virus that causes the disease. They wanted to see if the pathogens would change and weak forms might rise.

They eventually paralyzed versions of the polio virus that could still make people sick but did not cause paralysis. Sabin, also known as mild weakness, has become the oral vaccine for oral paralysis given to a cup of sugar to billions of children.

Now, researchers say, synthetic biology has led to a weak form of the pandemic coronavirus that causes covid-19. Although this idea has been around for a long time in the vaccine competition, an added coronavirus can be formulated for use worldwide in cheap noses.

The start-up company behind the new version of SARS-CoV-2, called Codagenix, is working with the Indian Serum Institute, based in Pune, which considers itself to be the largest injector manufacturer in the world. The plans are for volunteers to be the first to crack down on the virus, which was made synthetically in November, during initial human security tests in the UK.

Candidates for the most advanced vaccines, including AstraZeneca and Modern Pharmacists, treat a person with just one piece of the virus, the “spike” crown that bears his or her name, to make antibodies.

The potential advantage of vaccination using a live vaccine is that the body will be exposed to the virus — and will be able to respond. People will “catch up” with their noses, and it will still grow inside them. In theory, it can produce not only antibodies in the nasal passage but also T cells and specific types of protection, and may lead to broader protection.

One might imagine that one would intentionally get infected with the coronavirus, but tin-virus vaccines are common. The FluMist pediatric influenza vaccine contains a weak influenza virus. The Serum Institute sells 750,000 doses of live measles vaccines a year. The only disease that has ever been successfully removed from the gut, pelox, has been cleared with live virus shots.

“If you want to complete the immunological response, then you need to imitate the path of the disease,” says Rajeev Dhere, director of the Serum Institute. “This can only be done with a mild live vaccine.”

The virus recreates

In the past, finding a weak spot to be used for vaccination was a painful process, says Stanley Plotkin, who advises Codagenix and participated in early polio research. This is because it occurs with the growth of a virus in cells from other species and is waiting for a weaker chance to appear. It can take up to 10 years. Sometimes a tension with a moving gun is never seen.

A new, rational approach emerged in 2002. Then Eckard Wimmer, a virologist at Stony Brook University, caused a sensation by creating an infectious polio virus starting only from genetic instructions. According to the newspaper headlines it was “the first creation of life in a test tube”, and also a potential bioterror threat.

Some called Wimmer’s protest irresponsible. But technology for producing viruses from data also allows researchers to be creative, because the process allows them to by any means they want to rewrite the genes of the virus. Farren Isaacs, a biologist at Yale University, says: “This is where synthetic biology comes in. Genome modification. You can take the evolution that has lasted for years, for days.” “Unfortunately, the pandemic creates an opportunity for this technology.”

Instead of creating dangerous microbes, by 2008 Wimmer and J. Robert Coleman, then his lab member and now CEO of Codagenix, began demonstrating how they could use synthetic biology to design weaker versions of polio. a strategy they called “synthetically attenuated virus engineering” or, more colloquially, “death by the thousands.”

To understand how they do this, one needs to know that genes work using a three-type code. To make proteins, a cell looks at these three “codon” codes to determine which amino acid is next to the protein it builds. But it turned out that the genetic code has increased. There are 64 codons that can be written in the genetic alphabet, but only 20 amino acids are produced. For example, four codons encode the same amino acid, serine.

The way evolution has also gained increasing importance. All life uses the same methods, but depending on whether you are a bacterium, a human, or a star, you will have a preference for using certain codons or cot codons.

Viruses that steal cells to copy their proteins have, presumably, developed a taste for the same codons that human cells prefer. But processing options can be reversed in the laboratory, in a process that Codagenix calls “deoptimization.” Coleman says the company has created versions of the coronavirus whose genes have been fragmented into 240 mutations that give it several codons that give it the worst performance.

The result: the engineering virus looks exactly the same on the outside but has a “virtual fan pedal” inside it, causing it to recur much less quickly. The coronavirus can typically make up to 100 million copies inside a cell in a single day, but Coleman says the deoptimized version will make up half of its copies in the lab. Within an individual, it can be less than a factor of up to 1000, so that the defense system responds in time.

Some scientists do not see a role for live vaccination in the covid-19 war. “This is a stupid virus that fights vaccination,” says Michael Farzan, an expert at the Scripps Research Institute. He says the virus highlights its most important weakness, the spike protein, in a way that makes it a target target for antibodies, which other vaccines can make. “Only when you do not have a safe virus do you need live viruses. In this case it poses a risk that is not needed. There is no need for a live virus to grow inside you.”

The Serum Institute, which typically sells injections in the developed world, is working to develop four potential coronavirus injections, including competitions at Oxford University and Novavax, a biotech company in the United States. These are in the advanced stages of testing, but there is no guarantee that they will work, and there may be supply gaps.

Dhere refers to live vaccination as something like a rescue plan of the Serum Institute. Vaccines like this are made using old, built-in technology, and are delivered without injection. “Oral polio vaccination is very successful around the world because it’s a few drops in a child’s mouth. You do not need large medical devices,” he says. “So we felt that during a pandemic, the best version. “The simplest thing about a vaccine is that it can reach billions of cases. When it reaches a mass level, we think it will be the best approach.”

Transfer risk

What are the risks? The tuberculosis virus can still be dangerous for people with broken immune systems. Another risk is that a weakened virus can “return” to its more dangerous form. “We’re always wondering if he’ll be back,” Coleman says.

That can be caused by polio. In recent decades, vaccine pains have become more common than the wild virus. According to Plotkin, because only “relatively small” mutations separate Sabin’s vaccine pains from wild-type polio, and the endangered virus (which spreads within humans and even spreads among them) can eventually return to form. its proper.

In contrast, the virus crown “deoptimizes” several hundred genetic changes. The chances of success finding a way to break up a part of them are also mathematically limited. “I think it ‘s not possible,” says Dhere.

Instead of injecting the needle back into a dangerous form, Dhere says a bigger risk is that the wild-type coronavirus will change in ways that make some injections less effective. Coronavirus has not changed much so far: in fact, it was surprisingly stable. However if the spike protein is altered, the main candidate vaccines may be less effective because they only target that molecule.

A high-risk live vaccine — because it contains all parts of the virus — may not be a problem. “We don’t want to change the virus if it does,” he says. But if it does, “we will still have a vaccine that still looks 99%.”


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