Smartphones, superglue, electric cars, video chat. When does the miracle of new technology disappear? When you get so used to his presence that you don’t think about him anymore? When something newer and better appears? When you forget how things were before?
Whatever the answer, CRISPR gene editing technology has not yet reached that point. Ten years after Jennifer Dudna and Emmanuel Charpentier first presented their discovery at CRISPR, it remains at the center of ambitious research projects and complex ethical discussions. He continues to create new avenues for research and to renew old research. It is used by biochemists, as well as other scientists: entomologists, cardiologists, oncologists, zoologists, botanists.
Cathy Martin, a botanist at the John Ines Center in Norwich, England, and Charles Xavier, founder of the X-Men superhero team: They both love mutants.
But while Professor X has an affinity for superpowered human mutants, Dr. Martin is addicted to the red and juicy type. “We’ve always craved mutants because it allowed us to understand functionality,” said Dr. Martin of his study, which focuses on plant genomes in hopes of finding ways to make foods – especially tomatoes in her case – healthier. , stronger and longer lasting.
When CRISPR-Cas9 appeared, one of Dr. Martin’s colleagues offered to make her a mutant tomato as a gift. She was a little skeptical, but told him, “I’d really like a tomato that doesn’t produce chlorogenic acid,” a substance thought to have health benefits; tomatoes without it had not been found before. Dr. Martin wanted to remove what she believed was the key gene sequence and see what happened. Soon there was a tomato in her lab without chlorogenic acid.
Instead of looking for mutants, it was now possible to create them. “Getting these mutants was so effective and it was so wonderful because it confirmed all these hypotheses we had,” Dr. Martin said.
More recently, researchers in Dr. Martin’s lab used CRISPR to create a tomato plant that can accumulate vitamin D when exposed to sunlight. Just one gram of leaves contains 60 times the recommended daily value for adults.
Understand sickle cell disease
The rare blood disease, which can cause debilitating pain, strokes and organ failure, affects 100,000 Americans and millions of people worldwide, mostly in Africa.
Dr. Martin explained that CRISPR can be used in a wide range of food modifications. It can potentially remove allergens from nuts and create plants that use water more efficiently.
“I’m not saying that what we did with vitamin D will solve the problem of food insecurity,” said Dr. Martin, “but it’s just a good example. People like to have something they can hold on to, and that’s it. That’s not a promise. “
Infectious disease
Transfer of tests to remote parts of Africa
Christian Happi, a biologist who heads the African Center for Excellence in Infectious Disease Genomics in Nigeria, has spent his career developing methods to detect and limit the spread of infectious diseases that spread to humans from animals. Many of the existing ways to do this are expensive and inaccurate.
For example, to perform a polymerase chain reaction or PCR test, you need to “extract RNA, have a machine that costs $ 60,000, and hire someone who is specially trained,” Dr. Happy said. At the same time, it is expensive and logistically implausible to conduct this type of testing in most remote villages.
Recently, Dr. Happy and his colleagues used CRISPR-Cas13a technology (a close relative of CRISPR-Cas9) to detect diseases in the body by targeting genetic sequences associated with pathogens. They were able to sequence the SARS-CoV-2 virus within weeks of the pandemic’s arrival in Nigeria and develop a test that requires no on-site equipment or trained technicians – just a spit tube.
“If you’re talking about the future of pandemic preparedness, that’s what you’re talking about,” Dr. Happy said. “I would like my grandmother to use this in her village.”
The CRISPR-based diagnostic test works well in the heat, is fairly easy to use, and costs one-tenth of the standard PCR test. However, Dr. Happy’s lab is constantly evaluating the accuracy of the technology and trying to persuade leaders in African public health systems to accept it.
He called their offer one that “is cheaper, faster, requires no equipment and can be passed to the most remote corners of the continent.” This would allow Africa to occupy what I call its natural space.
Hereditary disease
Search for a cure for sickle cell disease
In the beginning there was nuclease on zinc soil.
It was the gene editing tool that Gang Bao, a biochemical engineer at Rice University, first used to try to treat sickle cell disease, a hereditary disease marked by deformed red blood cells. It took Dr. Bao’s lab more than two years to develop, and then the zinc soil nuclease would successfully reduce the crescent cell sequence by only about 10 percent of the time.
Another technique took another two years and was only slightly more effective. And then, in 2013, soon after CRISPR was used to successfully edit genes in living cells, Dr. Bao’s team changed course again.
“From the beginning until we got some initial results, CRISPR took us about a month,” said Dr. Bao. The method successfully cuts the target sequence about 60 percent of the time. It was easier to do and more efficient. “It was just amazing,” he said.
The next challenge was to determine the side effects of the process. That is, how did CRISPR affect genes that were not targeted? After a series of animal experiments, Dr. Bao is convinced that the method will work in humans. In 2020, the Food and Drug Administration approved a clinical trial led by Dr. Matthew Porteus and his laboratory at Stanford University, which is ongoing. It is also hoped that with the flexibility of CRISPR, it can be used to treat other inherited diseases. At the same time, other treatments that did not rely on gene editing have been successful for sickle cells.
Dr. Bao and his laboratory are still trying to determine all the secondary and tertiary effects of using CRISPR. But Dr. Bao is optimistic that safe and effective treatment for editing sickle cell genes will soon be available. How soon? “I think another three to five years,” he said, smiling.
cardiology
Peering into the secrets of the heart
It’s hard to change someone’s heart. And it’s not just because we are often stubborn and get in our way. The heart generates new cells at a much slower rate than many other organs. Treatments that are effective in other parts of the human anatomy are much more difficult for the heart.
It is also difficult to understand what is in someone’s heart. Even when you sequence an entire genome, there are often a number of segments that remain mysterious to scientists and physicians (called variants of uncertain significance). The patient may have heart disease, but there is no way to permanently link it to their genes. “You’re stuck,” said Dr. Joseph Wu, director of the Stanford Cardiovascular Institute. “So traditionally we’ll just wait and tell the patient we don’t know what’s going on.”
But in the last few years, Dr. Wu has used CRISPR to see what effects the presence and absence of these confusing sequences have on heart cells simulated in his laboratory with blood-generated induced pluripotent stem cells. By cutting out certain genes and observing the effects, Dr. Wu and his colleagues were able to draw connections between the DNA of individual patients and heart disease.
It will be a long time before these diseases are treated with CRISPR, but diagnosis is the first step. “I think this will have a big impact on personalized medicine,” said Dr. Wu, who mentioned that he found at least three variants of uncertain significance when he received the sequencing of his own genome. “What do these options mean to me?”
Sorghum is used in bread, alcohol and cereals around the world. But it is not commercially designed to the same extent as wheat or corn, and when processed, it is often not as tasty.
Karen Massel, a biotechnologist at the University of Queensland in Australia, saw plenty of room for improvement when she first began studying the plant in 2015. And since millions of people eat sorghum around the world, “if you make a small change, you can have a huge impact, “she said.
She and her colleagues have used CRISPR to try to make sorghum frost-resistant, heat-tolerant, extend its growth period, change its root structure – “we use gene editing everywhere,” she said. .
Not only can this lead to tastier and healthier cereals, but it can also make plants more resilient to changing climates, she said. But it is still no small task to accurately edit the genomes of cultures with CRISPR.
“Half of the genes we destroy just have no idea what they’re doing,” Dr. Massel said. “The second we try to get in there and play God, we realize we’re a little out of our depths.” But using CRISPR combined with more traditional breeding techniques, Dr. Massel is an optimist, although he is a self-described pessimist. And she hopes that further progress will lead to the commercialization of genetically modified foods, making them more accessible and acceptable.
In 2012, a 6-year-old girl suffered from acute lymphoblastic leukemia. Chemotherapy failed and the case was too advanced for a bone marrow transplant. There seemed to be no other option, and the girl’s doctors told her parents to return home.
Instead, they went to Children’s Hospital in Philadelphia, where doctors used an experimental treatment called T-cell therapy with a chimeric antigen receptor (CAR) to turn the girl’s white blood cells …
Add Comment