An example of the possibilities of CRISPR for treating sickle cell disease: A patient in China with HIV in a cancerous environment where the immune cells aren’t normal

Examples from across the world illustrate the possibilities of what CRISPR can accomplish. Two children were treated in China with it for a genetic condition related to sickle cell disease. Before treatment, the children were unable to create normal red blood cells and required blood transfusions every two to three weeks. Within a month after they received gene-edited cells, the transfusions ended. The children were completely free of disease symptoms eighteen months later.

Later this month, the volunteer will stop taking the antiretroviral drugs he’s been on to keep the virus at undetectable levels. If the virus recurs, investigators will wait a year. They will consider the experiment a success if it isn’t successful. “What we’re trying to do is return the cell to a near-normal state,” says Daniel Dornbusch, CEO of Excision BioTherapeutics, the San Francisco-based biotech company that’s running the trial.

The HIV virus attacks immune cells in the body called CD4 cells and hijacks their machinery to make copies of itself. Some HIV-ridden cells can be inactive for years, not producing new virus copies. There are major barriers to curing HIV.

That was an important step toward testing the treatment in people, says Kamel Khalili, a professor of microbiology at Temple University who led the work and is a cofounder of Excision Biotherapeutics. “You don’t want to eliminate the viral genome but at the same time cause any disruption in another part of the human genome and then create another set of problems for the patients,” he says. The area within HIV that we identified was not in the same place as the human genome.

They were able to confirm their findings after a number of analyses, and after using the genome editing technique to insert the T cell receptors into participants’ T cells. Each participant then had to take medication to reduce the number of immune cells they produced, and the engineered cells were infused.

The researchers then used algorithms to predict which of the mutations were likely to be capable of provoking a response from T cells, a type of white blood cell that patrols the body looking for errant cells. “If [T cells] see something that looks not normal, they kill it,” says Stephanie Mandl, chief scientific officer at PACT Pharma in South San Francisco, California, and a lead author on the study. At some point in the fight against cancer, the immune system lost the battle and the tumours started to grow.

“This is a tremendously complicated manufacturing process,” says Joseph Fraietta, who designs T-cell cancer therapies at the University of Pennsylvania in Philadelphia. The procedure in some instances took more than a year.

Although the efficacy of the treatment was low, the researchers used relatively small doses of T cells to establish the safety of the approach, says Ribas. “We just need to hit it stronger the next time,” he says.

When the engineered cells are infused, they will be more active and spend less time being cultured outside of the body. “The technology will get better and better,” says Fraietta.

The Discovery of CRISPR-Cas9 in a Viral Genome Does Not Depend on He, nor Does he Have the Experience

Fraietta said that the common surfaceprotein had not been found in solid tumours. Solid tumours give physical barriers to the T cells, which must circulate through the blood to get to the tumours and kill the cancer cells. Tumour cells can suppress the immune system by either releasing chemical signalling or using up the local supply of nutrients to fuel their growth.

Viruses sometimes pick up snippets of their hosts’ genomes, and researchers had previously found isolated examples of CRISPR–Cas in viral genomes. If the stolen genes give the virus a competitive edge, it could be kept and modified to serve the viral lifestyle. For example, a virus that infects the bacterium Vibrio cholera uses CRISPR–Cas to slice up and disable DNA in the bacterium that encodes antiviral defences2.

Some of these viral systems were capable of editing plants and mammals, and possess features that could make them useful in the laboratory.

“Each year we have thousands of new genomes becoming available, and some of them are from very distinct environments,” she says. “So it’s really going to be interesting.”

Nearly five years later, researchers tell Nature that they do not expect a similar revelation at this year’s summit — if only because He’s experience will dissuade rogue researchers from going public with controversial genome-editing experiments. But that doesn’t mean that such experiments aren’t happening: “I wouldn’t be surprised if there were other children that have been created with CRISPR–Cas9 in the years since 2018,” says Eben Kirksey, a medical anthropologist at the University of Oxford, UK.

Just as CRISPR once seemed to be something out of science fiction, so might everything in the preceding paragraphs — but every step of that process is technically feasible today.

There are up to 400 million people worldwide affected by one of the 7,000 diseases caused by mutations in single genes. The scientists owe their families honesty because of the chasm between an IV and a test tube. Technical, legal, financial and organizational are obstacles that can be overcome.

For their part, Kopp and Bartolome are thrilled. Kopp’s been in remission for more than two years. “You know, I’ve been a homeopathic all my life, pretty much, and now I joke … ‘I’m genetically modified,’ ” Kopp says so. “But this little vial of cells can change my life? Wow. It’s a medical miracle.

CAR T-cell Living Therapy for Cancer Immunotherapy: a Game-changer for the future, says Dr. Joseph McGuirk

Bartolome, a former NBA basketball player, was game, too. “It sounded like something from a science fiction movie. Bartolome says he thought that was cool.

“In contrast to drugs, this is a living therapy,” says Dr. Joseph McGuirk, an oncologist at the University of Kansas, who treated Kopp. “You’re injecting into your patient a drug that is alive, that can persist for weeks to months and sometimes beyond that — for years.” McGuirk and others are hoping CRISPR can make better CAR T-cell living drugs, such as versions that are more potent and effective at treating more common cancers.

It could be cheaper to use off-the-shelf CAR T-cell treatments. “I am really excited about this.” This would be a game-changer that way, with a total new approach,” says Dr. Carl June is a CAR T-cell pioneer at the University of Pennsylvania who is not involved in the studies that included Kopp and Bartolome.

“This is the most exciting — just extra-extraordinary — time in my entire career,” McGuirk says. I have always been enthusiastic by the work we’ve been doing. But this is unprecedented.”

“The prospects are much brighter than anyone could have dreamed of 10 years ago,” agrees Fyodor Urnov, a gene-editing scientist at the University of California, Berkeley, who was not involved in the research. “This field is moving very fast.”

More research is needed involving more patients to figure out how well the off-the-shelf approach works, how long it lasts and how to make the cells work better.

“When you consider the overwhelming number of these patients would have died, that’s a big advance,” McGuirk says. “None of us are satisfied with that. We need to do better. For example, he says, some of the shortcomings might be overcome by giving patients more than one infusion.

Source: https://www.npr.org/sections/health-shots/2022/12/13/1140384354/crispr-improves-cancer-immunotherapy-car-t-cell

The Third International Summit on Human Genome Editing : Implications for ethical research and medical research in the United States, UK, and beyond

Bartolome will always remember the day the doctors told him they couldn’t find any cancer in his body. That was more than a year ago. It was a life-changing event. And I was bubbling up inside, that’s for sure,” he says. “That was a great day. And every day since then I just thank my lucky stars.”

Scientists immediately recognized the value of base editing. A lot of inheritable diseases are caused by single- base changes in DNA. In theory, it would be possible to change one base for another. A team headed by Qasim wanted to use base editing to alter immune cells in order to treat cancer.

The patient, a 13-year-old named Alyssa, was diagnosed with a rare and aggressive type of cancer called T-cell leukemia in May 2021. T cells are the part of the immune system that protects against infections. But in T-cell leukemia, they grow uncontrollably. Doctors tried to treat Alyssa with chemotherapy and a bone marrow transplant, but her cancer came back.

When researchers gather in London next week for the Third International Summit on Human Genome Editing, they will discuss the latest advances in deploy techniques such asCas9 to treat genetic diseases, and look ahead to the possible approval of the first genome-editing therapy later this year.

The shadow cast by the previous summit will be difficult to shake despite the promising future. The meeting was convened just hours after He Jiankui announced that he had edited his embryo’s genomes so they could be used as living babies. The three years in prison for breaking China’s laws on medical experiments was the result of the stunt.

From a regulatory standpoint, many countries — including the United States — still do not have mechanisms to ensure that edited embryos are not implanted, says Kirksey. New guidelines were released by China on ethical conduct in research. These address the need to inform study participants about potential risks, and provide a detailed description of how ethical review boards should run, says Joy Zhang, a sociologist at the University of Kent in Canterbury, UK. But they still rely on the conventional model of medical research based at hospitals, research institutes and universities, she says. She says that private ventures or individuals can initiate a research project that can be quite damaging and cutting edge. We need to rethink how we govern.

National regulations don’t take into consideration the potential international scope of heritable genome editing, according to a human-rights lawyer at Mexico City’s National University of Mexico. “It’s not that there are no laws. She says there are many laws. “We need to change the approach to enforcement. This should be seen as an international jurisdiction.

The rising prices of gene therapies are making researchers worry that genome-editing treatments will also be too expensive for most of the world. The FDA approved a gene therapy that costs US$5 million per treatment. “There’s a lot of hope, but the hope has to be balanced a bit with the way things are going,” says Lovell-Badge.

One development that could facilitate access in low- and middle-income countries is the effort to expand vaccine-manufacturing capacity in the global south. Some vaccines rely on alipid nanoparticle to protect the strand of mRNA and get it to enter the cell. It’s possible that genome-editing therapies, which also use snippets of RNA, will involve similar delivery systems, says Musunuru, so could use the same fundamental technology. He says that if it wasn’t for the Pandemic, we wouldn’t be here. “If you had asked me five years ago if we could do the things we could do now, I would have said, ‘That would be amazing, but no.’”