Virus World

He Jiankui’s work was also carried out on a third infant, according to China’s state media, in a new disclosure that is likely to add to the global uproar over such experiments. A court in China on Monday sentenced He Jiankui, the researcher who shocked the global scientific community when he claimed that he had created the world’s first genetically edited babies, to three years in prison for carrying out “illegal medical practices.” In a surprise announcement from a trial that was closed to the public, the court in the southern city of Shenzhen found Dr. He guilty of forging approval documents from ethics review boards to recruit couples in which the man had H.I.V. and the woman did not, Xinhua, China’s official news agency, reported. Dr. He had said he was trying to prevent H.I.V. infections in newborns, but the state media on Monday said he deceived the subjects and the medical authorities alike.

Dr. He, 35, sent the scientific world into an uproar last year when he announced at a conference in Hong Kong that he had created the world’s first genetically edited babies — twin girls. On Monday, China’s state media said his work had resulted in a third genetically edited baby, who had been previously undisclosed. Dr. He pleaded guilty and was also fined $430,000, according to Xinhua. In a brief trial, the court also handed down prison sentences to two other scientists who it said had “conspired” with him: Zhang Renli, who was sentenced to two years in prison, and Qin Jinzhou, who got a suspended sentence of one and a half years. The court held that the defendants, “in the pursuit of fame and profit, deliberately violated the relevant national regulations on scientific and medical research and crossed the bottom line on scientific and medical ethics,” Xinhua said.

Dr. He’s declaration made him a pariah among scientists, cast a harsh light on China’s scientific ambitions and embroiled other scientists in the United States who were connected to Dr. He. Though Dr. He offered no proof and did not share any evidence or data that definitively proved he had done it, his colleagues had said it was possible that he had succeeded. American scientists who knew of Dr. He’s plans are now under scrutiny. Dr. He’s former academic adviser, Stephen Quake, a star Stanford bioengineer and inventor, is facing a Stanford investigation into his interaction with his former student. Rice University has been investigating Michael Deem, Dr. He’s Ph.D. adviser, because of allegations that he was actively involved in the project. Dr. Quake has said he had nothing to do with Dr. He’s work. Mr. Deem has said he was present for parts of Dr. He’s research but his lawyers have denied that he was actively involved. During the Hong Kong conference, Dr. He said he used in vitro fertilization to create human embryos that were resistant to H.I.V., the virus that causes AIDS. He said he did it by using the Crispr-Cas9 editing technique to deliberately disable a gene, known as CCR₅, that is used to make a protein H.I.V. needs to enter cells. he international condemnation from the scientific community that followed Dr. He’s announcement came because many nations, including the United States, had banned such work, fearing it could be misused to create “designer babies” and alter everything from eye color to I.Q.

A team of scientists led by Texas Biomed's Assistant Professor Smita Kulkarni, Ph.D. and Mary Carrington, Ph.D., at the Frederick National Laboratory for Cancer Research, published results of a study that pinpointed a long noncoding RNA molecule which influences a key receptor involved in HIV infection and progression of the disease.

Most of the genome is made up of noncoding RNAs which do not directly translate into proteins. In fact, 97% of the human genome is non-protein coding. Dr. Kulkarni says that until the last decade or so, scientists thought many of these particular RNAs were "junk." Now, new research shows they play many roles. Recent developments in technology and genomics have made advances in knowledge in this area possible.

Dr. Kulkarni and her colleagues showed that a specific long noncoding RNA impacts the gene encoding the HIV co-receptor CCR5. Since CCR5 is critical for the HIV virus to enter the cell, a polymorphism associated with variation in expression of this long noncoding RNA impact the infection's outcome. Genomic DNA from various groups including Hispanics, African Americans and Japanese showed that this association is present across many ethnicities. This consistency of this association across populations speak to a single functional mechanism explaining this association.

The findings were published in Nat. Immunology:

https://doi.org/10.1038/s41590-019-0406-1

Researchers identify a protein that stops the brain from connecting memories, and regulating it could help improve memory loss treatment.  Throughout our lives, significant events are saved by the brain’s neurons and stored as memories. But memories don’t sit alone. Normally, they are connected to a number of others, making a reasonable reconstruction of events in a rational timeline. “Real-world memories are formed in a particular context and are often not acquired or recalled in isolation,” wrote a group of scientists led by Alcino Silva from the University of California, Los Angeles (UCLA). “Time is a key variable in the organization of memories, as events that are experienced close in time are more likely to be meaningfully associated, whereas those that are experienced with a longer interval are not.” The team is interested in exploring mechanisms involved in memory formation to better understand the process of linking memories — how one memory can trigger the recall of another in a sequential series of events that took place within a certain period of time. In a recent study, the UCLA team reported that the activation of a protein called CCR5 acts as a biological switch that defines the size of the time window that connects subsequent memories together — manipulating it could lead to better memory loss treatment.

This was intriguing to the team as CCR5 is a protein found in immune cells and has been studied extensively as a result of the role it plays in the inflammatory response during HIV infections, as the virus uses it to enter human cells. “Discovering the involvement of CCR5 in memory was a surprise,” said Silva, professor of neurobiology and psychology at the UCLA. “Years ago, our research team was looking for ‘new’ proteins involved in memory, and to our amazement, we found that CCR5 was one of them.” In mouse models, they found that CCR5 activation in neurons of the hippocampus — a brain region involved in memory formation — stops connecting memories to one another in mice subjected to behavioral models of memory. The mice were exposed to two different events separated by an increasing period of time. The scientists observed that if CCR5 activation occurred in between both events, mice weren’t able to relate one event to the other, but when both events occured before CCR5 activation, the mice related the memory of the first event to the second.   The precise coordination of memory systems in the human brain is very important, as when dysfunction in memory linking occurs it can lead to problems which manifest in diseases such as dementia, schizophrenia, and Alzheimer’s disease. “There are so many causes for memory loss affecting the lives of millions of people and there’s so little that we can do for them,” said Silva. “Memory dysfunction can appear in cases of post-traumatic stress disorder, depression, and even in patients undergoing cancer treatment.”

Gradual memory loss also occurs naturally during aging — an event that also occurs in mice.  As a result, the team used a middle-aged mouse model to study how CCR5 manipulation could help improve memory loss treatment in this scenario. The solution presented itself in the form of a drug named maravidoc, which blocks the activity of CCR5 and has been used to treat HIV infection where the molecule binds CCR5 proteins, interfering with virus’ ability to enter cells. After treating middle-aged mice with the drug, they observed that the size of the time window in which mice could link memories together was extended, and their memory recovered similar features to those seen in younger mice. “When we used maraviroc, we were able to reverse the memory deficits in middle-aged mice,” said Silva. This discovery suggests that maravidoc could be a potential memory loss treatment to help people suffering from memory dysfunction. Repurposing maravidoc could be straight forward as it is already in clinical use and has been proven to be safe over long periods of time in patients with HIV. Importantly, different studies have shown that maravidoc reaches the brain when given systemically, providing an opportunity to target CCR5 in neurons without the need for invasive procedures. “There’s a great need for memory drugs,” said Silva. “The few memory drugs that are being used in the clinic help patients, but with a very little effect. The wonderful thing about this study is that we already know that maravidoc is relatively safe and it’s very likely that people suffering from memory deficits may be able to use it for extended periods of time.”

Cited article published in Nature (May 25, 2022):

 https://doi.org/10.1038/s41586-022-04783-1 

For the first time, a patient got treated for HIV and cancer at the same time, with an infusion of gene-edited stem cells. The results? Mixed. Imagine you’re 27 years old and you start feeling ill. Ill enough that you go to the hospital, and after much poking and prodding and waiting for lab results you learn you’re HIV-positive. Two weeks later you find out that’s not even the worst of it. You’ve got leukemia too.

Under any circumstances it would be a lot to take in. Especially in China, where HIV/AIDSis highly stigmatized. But for one young man living there, who this happened to in the late spring of 2016, there was one small but significant silver lining to this double whammy of a diagnosis. He would be eligible to participate in the first-ever clinical trial to assess the safety of trying to cure both the cancer and the infection in a single procedure using the gene editing tool call Crispr. In July of 2017, doctors in Beijing blasted the patient with chemicals and radiation to wipe out his bone marrow, making space for millions of stem cells they then pumped into his body through an IV. These new stem cells, donated by a healthy fellow countryman, would replace the patient’s unhealthy ones, hopefully resolving his cancer. But unlike any other routine bone marrow transplant, this time researchers edited those stem cells with Crispr to cripple a gene called CCR5, without which HIV can’t infiltrate immune cells.

Now, more than two years later, the patient is in good health, his cancer in full remission, as researchers report today in the New England Journal of Medicine. The edited stem cells survived and are still keeping his body supplied with all the necessary blood and immune cells, and a small percentage of them continue to carry the protective CCR5 mutation. Not enough to have cured him of HIV, though—he remains infected and on antiretroviral drugs to keep the virus in check. Still, experts say the new case study shows this use of Crispr appears to be safe in humans and moves the field one step closer toward creating drug-free HIV treatments.

“The safety profile appears to be acceptable,” pioneering cancer researcher Carl June wrote in an accompanying editorial, noting that the editing appeared to be precise, and that the engineered stem cells didn’t provoke an immune response in the patient. June did offer a caveat that the study’s single patient offered only limited data to draw on. What he found more striking was how quickly the science has moved from the first reports of using Crispr to treat HIV infection in mice to trying it in humans: only two years. At the University of Pennsylvania, June has led work in  a ground-breaking cancer treatment called CAR-T, which involves genetically reprogramming immune cells into a clone army of tumor-targeting assassins. But it took him five years to go from studies in animals to trials involving humans. In this case, China’s more permissive biomedical research regulations might have expedited the work, or it could be that genetic engineering is lending new momentum to the race for an HIV/AIDS cure, he wrote. “In any case, the genie is out of the bottle with genome editing.”

This is the first time an HIV-positive patient has been treated with Crispr-edited cells. But scientists have been trying to find ways to genetically disable CCR5 for more than a decade now. It all started in 2007, when a German doctor took a 41-year-old man with HIV/AIDS and leukemia off of his antiretroviral drugs and hooked a thin tube up to a vein in his chest. Through it, the so-called Berlin Patient received blood cells from a bone marrow donor who had a naturally occurring mutation called CCR5 Δ32. He was missing a chunk of DNA that ultimately allows an HIV virus to enter immune cells. The patient survived his cancer and became the first (though no longer the only) person considered to be fully cured of HIV/AIDS....

The study was published on September 11, 2019 in the New England Journal of Medicine:

https://doi.org/10.1056/NEJMoa1817426