Crispr was used to cure HIV

Treatment of HIV through genetic engineering of a cell-generated reservoir: the case of Khalili’s Excision Biotherapeutics

The researchers at the University of Nebraska and Temple University discovered that Crispr was able to remove HIV from mice’s genomes. The approach was able to remove SIV from macaques, the primate version of HIV, after a year.

Later this month, the volunteer will stop taking the antiretroviral drugs he’s been on to keep the virus at undetectable levels. Then, investigators will wait 12 weeks to see if the virus rebounds. If the experiment goes well, they will consider it a success. Daniel Dornbusch, the CEO of Excision BioTherapeutics, says that they are trying to restore the cell to a normal state.

The HIV virus attacks immune cells in the body called CD4 cells and hijacks their machinery to make copies of itself. But some HIV-infected cells can go dormant—sometimes for years—and not actively produce new virus copies. These so-called reservoirs are a major barrier 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. He says that eliminating the viral genome would cause any disruption in another part of the human genomes and create other problems for the patients. We needed to find a place within HIV that didn’t clash with the human genome.

To create these cells, doctors can reprogram the T cells in a healthy donor’s body to do three things: leave alone the healthy cells in a patient’s body, hide the recipient’s own immune system, and zero in on them.

The researchers used an mathematical method to figure out which of the five genes could cause the T cells to respond. “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 times the immune system of patients with cancer can be lost, and this leads to the growth of the tumours.

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

“The results so far are encouraging,” Sadelain says. “However, the rate of responses is not as good as you obtain with a patient’s own cells. So we need further investigation.”

And as researchers develop ways to speed up the therapies’ development, the engineered cells will spend less time being cultured outside of the body and could be more active when they are infused. “The technology will get better and better,” says Fraietta.

Genome editing in solid tumours is not a fantasy, but a reality: How far can you go? A case study of the CRISPR-Cas genome

But common surface proteins have not been found in solid tumours, says Fraietta. Solid tumours have physical barriers to T cells that must travel through the blood to the tumours and kill the cancer cells. Tumour cells also sometimes suppress immune responses, both by releasing immune-suppressing chemical signals and by using up the local supply of nutrients to fuel their rapid growth.

A group of people, including a biologists and a microbiologists, decided to do a more extensive search for the genes that make up the CRISPR–Cas systems. About 6,000 of them, including representatives of every known type of CRISPR–Cas system, were found by them. “Evidence would suggest that these are systems that are useful to phages,” says Doudna.

The viral system that was capable of editing the plant and mammal genomes possessed features that made them useful in the laboratory, such as compact structure and efficient editing.

Thousands of new genomes become available each year, and some come from very distinct environments. It is 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. Kirksey says that he would not be surprised if other children were created with the same technology in the years to come.

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 who are affected by a single disease caused by a single genes. Scientists owe their families honesty about the difference between a test tube and an IV line in a hospital. The greatest obstacles are not technical but legal, financial and organizational.

After a round of chemotherapy and a stem cell transplant, Katie Pope Kopp was diagnosed with a non- Hodgkin’s lymphoma. But nothing could beat it. In May of 2020 I went back to get a x-ray and they found my Non- Hodgkin’s had exploded back up, which was very disappointing.” She was originally diagnosed five years ago. Victor Bartolome underwent decades of treatment to keep his blood cancer at bay. Eventually, his doctors told him he had run out of options. “That was devastating. Imagine having what you think is your last hope pulled out from under you,” says Bartolome, 74, of Santa Barbara, Calif. Some doctors have started using the gene-editing technique CRISPR to modify cells of the immune system to try to fight cancer, as a result of hearing about something new. Kopp jumped at the chance to volunteer for a study testing the approach, even though she says she’s a tarot card reader who long relied on homeopathy instead of mainstream medicine.

CAR T-cell living drugs are not always the best therapy for cancer patients: A comment on Dr. Joseph McGuirk, Ph.D., a CRISPR pioneer

Bartolome played basketball in the NBA. “It sounded like something from a science fiction movie. I thought that was pretty cool,” Bartolome says.

Drugs are not always the best therapy for patients according to Dr. Joseph McGuirk of the University of Kansas. “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.

Off-the-shelf CAR T-cell treatments could also be much less expensive than custom-made. I’m so excited about this. Carl June is a CAR T-cell pioneer and is not associated with the studies that included Kopp and Bartolome.

McGuirk says this is the most exciting time in his career. I’ve always liked the work we’ve been doing. This is not normal.

“The prospects are better than 10 years ago, even though I was not involved in the project,” noted the scientist, who is not involved in the research. The field is moving very fast.

There needs to be more research into how well the off-the-shelf approach works and how long it lasts, in order to make the cells work better.

That’s a big advance when you consider the number of patients that would have died. We are not 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 first chemical base editor to change the gene: Bartolome explains the day T-cell leukemia doctors told him to stop noticing

Bartolome say he’ll never forget the day the doctors told him they couldn’t find a trace of 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 wonderful day. Since that time, I have just thanked my lucky stars.

The genetic code of every living thing is made up of a string composed of four chemical bases: A, C, G, and T. The double helix structure of the DNA can be formed by these pair. Traditional Crispr and previous gene editing methods work by cutting DNA’s double-stranded helix in order to knock out a disease-causing gene, for instance. Base editing simply swaps one chemical base for another in order to change a genes function. The first base editor that could convert a C to a T has been invented.

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 normally used to protect the body from infections. But in T-cell leukemia, they grow uncontrollably. Doctors tried to treat her cancer with treatments, but it returned.

Heritable Genome Editing in the United States, a burdensome challenge for medical research in the coming decade and a half: What is waiting for in Mexico?

The University of Pennsylvania has been developing a genome-editing therapy for the genetic disease for thepast year and a half. The team doesn’t involve creating double-strand breaks in the DNA, unlike the original CRISPR–Cas9 system. It is hoped that these techniques, called base editing and prime editing, can yield safer genome-editing therapies. But Musunuru says it is important to tackle the affordability question early in development. He says he sees an enormous potential for unfairness.

Despite that tantalizing future, it will be impossible to shake the shadow cast by the previous summit, in 2018. That meeting convened just a day after biophysicist He Jiankui announced that he had edited the genomes of three embryos that developed into living babies. He was sentenced to three years of prison for breaking the laws on medical experimentation in China.

Government research funding restrictions might have a negative effect on the behavior of researchers. Since being released from prison, he has been trying to get private investors to back his new project for a gene therapy. He Jiankui had a big question about the growing number of scientific practices that are outside of conventional scientific institutions. How do we know where they are?

Furthermore, national regulations do not take into consideration the possible international scope of heritable genome editing, says María de Jesús Medina Arellano, a human-rights lawyer at the National Autonomous University of Mexico in Mexico City. There are laws, it is not that there are no laws. She says there are many laws. “We need to change the approach to enforcement. This should be considered an international jurisdiction.”

The prices for existing gene therapies are too high, which may make genome-editing therapies much more expensive for the world. In November, the US Food and Drug Administration approved a gene therapy to treat haemophilia that has been priced at US$3.5 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.

Efforts to improve vaccine manufacturing capacity in the south could help facilitate access in low- and middle-income countries. Some vaccines rely on a triglyceride to protect the strand from the vacuole and allow it to penetrate the cell. It is possible that the same delivery systems used in the genome-editing therapies could also be used with the same technology. “If it hadn’t been for the pandemic, we wouldn’t be where we are,” he says. If you asked me a few years ago if we could do all the things that we can do now, I would have said no.