CRISPR could create a one-shot treatment for HIV

Here’s the thing about HIV: While we can suppress it with drugs, we can’t eliminate it. And while we can treat it so that the virus isn’t even transmissible — if the drugs are taken correctly — we can’t vaccinate against it.

That’s because HIV has some tricky skills that keep it one step ahead of the immune system, including the ability to hide in cells and its rapid mutation, making for a moving target that’s harder to hit than a late round of duck hunting

Therefore, researchers are looking for different approaches to tackle the virus, including new approaches to vaccines powered by mRNA and stimulating special immune cells called B cells.

HIV has multiple tricks for staying one step ahead of the immune system; we can control the virus, but not clean it up.

Antibody factories: B cells act like tiny antibody factories, releasing the proteins that fight viruses like HIV. But not all antibodies are created equal.

What researchers want to create is a class of antibodies called “broad neutralizing antibodies” (bNAbs), which can paralyze multiple variants of HIV, in all their rapidly mutating forms. But this is very difficult to do with vaccines, because you need the right kind of vaccine design to get the body to make the right kind of antibodies.

Researchers know how to use gene editing to directly program B cells to produce bNAbs, but they have to do it Outside of the body, in the lab – and that’s a problem.

B cells are like little antibody factories, fueling the pathogen-fighting proteins.

Unlike a vaccine or a drug, which has the same formulation for everyone, this would require a personalized treatment for each individual: extracting cells from each patient and then isolating, modifying, multiplying and re-infusing them.

To use such therapy clinically requires specialized medical centers and complicated protocols.

But in a new study in Nature Biotechnology, Tel Aviv University researchers found a way around this, by editing B cells to produce broadly neutralizing antibodies. inside the bodies of live mice.

It means that the same gene therapy could in principle be applied to everyone.

“Until now, only a few scientists, including us, had been able to manipulate B cells outside the body, and in this study we were the first to do this in the body and get these cells to generate the desired antibodies. Tel Aviv’s Adi Barzel told GEN.

Special antibodies called “broadly neutralizing antibodies” can paralyze multiple variants of HIV.

Virus vs Virus: To make their engineered B cells in vivothe researchers turned to one of genetics’ favorite friends: adeno-associated viruses (AAVs).

AAVs are excellent transmitters of genetic information: they are easy to reprogram, do not cause disease in humans, can target specific types of cells, and do not trigger a strong immune response.

But they’re also quite small, so the researchers used two to work as a team.

One virus carried the code for CRISPR-Cas9, everyone’s favorite genetic scissors; the other carried the code for HIV-fighting bNAbs.

“When the CRISPR cuts the desired site in the genome of the B cells,” doctoral student and study author Alessio Nehmad told GEN, “it directs the introduction of the desired gene: the gene that codes for the antibody against the HIV virus, that causes AIDS.”

When mice were injected with the AAVs, they did the trick by modifying B cells to produce bNAbs — all within the body. When the resulting antibodies were extracted from the blood of the mice, they proved effective at neutralizing HIV in a dish.

Using CRISPR and a few viruses, the researchers developed b cells to make the desired antibodies.

Interior design: While not ready for human trials, the ability to create modified B cells through genetic therapy in a patient is an exciting prospect.

“We have developed an innovative treatment that can defeat the virus with a single injection, with the potential to bring about a huge improvement in the patient’s condition,” the researchers told GEN.

And because the B cells replicate every time they skirmish with HIV, the therapy can create a feedback loop, with the treatment actively evolving to keep up with the virus.

The researchers believe the technique could also lead to new treatments, not only for HIV, but also for other diseases, including cancers derived from viruses.

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