Tag Archives: CCR5

Chinese Researchers Experiment with Making HIV-Proof Human Embryos

Yes, you read that headline correctly!


Chinese fertility doctors have tried to make HIV-proof human embryos, but the experiments ended in a bust. The new report is the second time researchers in China revealed that they had a go at making genetically modified human embryos.

The controversial experiments are, in effect, feasibility studies of whether it’s possible to make super-people engineered to avoid genetic disorders or resist disease.

“It is foreseeable that a genetically modified human could be generated,” according to Yong Fan, a researcher at Guangzhou Medical University, who published the report.

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His team collected more than 200 one-cell embryos and attempted to alter their DNA to install a gene that protects against HIV infection. The study, published two days ago in an obscure reproductive journal, was first spotted by reporters at Nature.

The scientists cautioned that they believe making actual genetically modified babies should be “strictly prohibited”—but perhaps only until the technology is perfected. “We believe that is necessary to keep developing and improving the technologies for precise genetic modification in humans,” Fan’s team said, since gene modification could “provide solutions for genetic diseases” and improve human health.

The Chinese scientists tried to make human embryos resistant to HIV by editing a gene called CCR5. It’s known that some people possess versions of this gene which makes them immune to the virus, which causes AIDS. The reason is they no longer make a protein that HIV needs to enter and hijack immune cells.

Doctors in Berlin demonstrated the effect after they gave a man sick from HIV a bone marrow transplant from a person with the protective gene mutation. The man—known since as the “Berlin patient”—was cured of HIV, too.

Using the gene-editing method called CRISPR, Fan and his team tried to change the DNA in the embryos over to the protective version of the CCR5 gene in order to show, in principle, that they could make HIV-proof people.

Almost exactly a year ago, in a world first, a separate group in Guangzhou said that it had altered embryos in an effort to repair the genetic defect that causes a blood disease beta thalassemia.

That set off an ethical debate, and last December the U.S. National Academy of Sciences, along with British and some Chinese scientific leaders, said any attempt to make a gene-edited baby would be “irresponsible,” a message that in many ways seemed directed at IVF doctors in China.

In February, U.S. officials went further, calling gene-editing a “weapon of mass destruction” and making a point of singling out the earlier Chinese research.

One day endowing people with protective genes could become a real possibility. It would be like a vaccine, except one that is installed in a person’s genome from birth. And there’s a long list of genes people might demand for their children in addition to HIV resistance. One DNA change, for instance, seems to completely prevent Alzheimer’s. Another generates people with twice the muscle mass.

But that’s a ways off, and Fan’s team said its experiments essentially flopped. They only managed to successfully edit a handful of embryos, and even these ended up as “mosaics,” or a mix of cells, some of which had the new gene, and some that didn’t.


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Another GIANT Leap Forward in the Search for a Cure for HIV

In a breakthrough six years in the making, an international team of researchers has determined the precise atomic structure of a cell-surface receptor that’s used by most strains of HIV to infect human immune cells. The finding could result in medicines that block the process.

HIV researchers have been making great strides recently — and thank goodness for that. Since making its unwelcome debut in the early 1980s, HIV/AIDS has killed more than 28 million people worldwide, with more than 34 million people currently living with the virus infection.

Back in March, scientists functionally cured a baby infected with HIV. A week later, doctors announced that a similar technique had effectively cured 14 adults. And late last year Canadian researchers announced that their efforts to create the world’s first HIV vaccine had cleared a major hurdle after a successful Phase I trial. Relatedly, it was only yesterday that researchers from Oregon Health & Science University announced that they have developedan HIV/AIDS vaccine that can completely clear an AIDS-causing virus from the body. There’s even a drug, called Truvada, that’s proven to reduce the risk of HIV infection.

Visualization = Understanding

The target is a receptor called CCR5 — and it’s one of two main entry points that HIV uses to launch its attack on the human immune system; CCR5 is a protein on the surface of white blood cells that’s involved in the immune system, acting as a receptor for chemokines (signalling proteins secreted by cells). After binding to it, an HIV protein fuses to the cell membrane beneath as it digs its way inside the cell. Infection ensues.

The other receptor that performs this feat is CXCR4. Together, the two belong to a family of receptor proteins called G-protein-coupled receptors (GPCRs) which regulate a host of functions in the human body. These receptors are crucial to scientists when designing drugs.

Until now, however, scientists haven’t been able to properly visualize the precise molecular structure of these labyrinthine receptors. Previous studies have successfully solved CXCR4’s structure, but the exact way it recognizes and binds to HIV viral proteins has remained a mystery.

Indeed, without a hi-res molecular “picture” of the receptors, designing drugs is difficult — if not impossible.

New discovery brings us one step closer to preventing HIV infections

Maraviroc to the Rescue

To capture the high resolution, three-dimensional atomic structure of the receptors, a team supported by both US and Chinese research agencies (including The Scripps Research Institute in California) considered Maraviroc, an antiretroviral drug and entry inhibitor used to treat HIV-1. It’s a receptor antagonist that binds the co-receptor, making it unavailable to circulating HIV.

New discovery brings us one step closer to preventing HIV infections

In this artistic impression, the HIV drug Maraviroc grabs hold of CCRF in an inactive configuration, preventing HIV from using the receptor to enter cells. (Courtesy of the Wu lab)

In the new study, the researchers demonstrated the precise spot where Maraviroc attaches to cells and blocks HIV’s entry.

Maraviroc was used by the researchers to bind an engineered CCR5 receptor. It was then purified and crystallized, resulting in a receptor/drug complex that measured 2.7 Angstroms. By looking at this bound complex at such a high resolution — where the receptor was made inactive and unresponsive to HIV — the scientists were able to catch a glimpse of the molecular pathway by which HIV fuses with cells, including the molecular-scale quirks that allow some strains of HIV to escape CCR5 inhibitors.

New discovery brings us one step closer to preventing HIV infections

Image: CCR5 side-by side with alternate HIV co-receptor CXCR4. (Courtesy of the Wu lab)

The study, which appears in Science, will help scientists to both improve existing HIV drugs based on CCR5 inhibition and to design new drugs altogether.

“We hope that the structure we determined can be used to understand the molecular details of the current viral strains of HIV entry, to develop new molecules that can inhibit both CXCR4 and CCR5 receptors, and to block future strains that might emerge and be addressed with second generation HIV entry inhibitors,” noted Beili Wu, a researcher from the Chinese Academy of Sciences’ Shanghai Institute.

via i09 Read the entire study at Science Express .

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