An improved gene-editing tool to fight cancer is undergoing clinical trials, reports Nature:
A high-precision successor to CRISPR genome editing has reached a milestone: the technique, called base editing, has made its US debut in a clinical trial. The trial tests more complex genome edits than those performed in humans so far.
Trial organizers announced on 5 September that the first participant had been treated using immune cells with four base-edited genes, equipping the cells to better target and destroy tumours. The hope is that the approach can tame trial participants’ difficult-to-treat form of leukaemia and serve as a gateway to more complex edits in the future…It’s been a strikingly quick evolution from the first reports of base editing in 2016 to clinical trials…while researchers develop ever more intricate gene-editing therapies, they are also keeping a wary eye on drug regulators in the United States and Europe. Officials in both places are expected to decide this year whether to approve the first CRISPR–Cas9 therapy, a treatment for sickle-cell disease.
That decision “will clarify for the field what needs to happen to meet the bar with regulators”, says John Evans, chief executive officer of Beam Therapeutics, the base-editing company..
Base editing’s appeal lies in its specificity and potential safety. The most common form of CRISPR–Cas9 genome editing relies on an enzyme called Cas9. Inside cells, Cas9 cuts both strands of the DNA double helix at a particular site. The cell’s DNA repair machinery then mends the cut, sometimes inserting or deleting a few DNA letters, or ‘bases’, as it does so. Such mistakes during repair often disable the gene, which is handy for some gene-editing applications. But researchers cannot control exactly how the cell repairs its DNA, and cannot predict the resulting DNA sequence.
Base editing, by contrast, generally cuts only one strand of DNA, and the base editor converts DNA bases at the break site to a particular type. The result is more control over the edited sequence, and less cell death from damaged DNA.
This has also opened the door to creating multiple edits in the same cell. Such multi-site editing can be risky with CRISPR–Cas9, because each edit requires breaking both strands of DNA. Multiple double-stranded breaks can create a mix of genomic fragments that the cell might not be able to properly stitch back together. The result can be a dangerous level of genomic chaos, with pieces of chromosomes in the wrong order or location — or missing altogether…
Beam Therapeutics and another research team, led by Qasim, are attempting to improve CAR-T-cell therapy, which is already used to treat a variety of cancers. It typically involves removing a sample of a person’s own T cells, engineering them to produce cancer-targeting proteins called chimeric antigen receptors (CARs) and then reinfusing the cells into the body.
The therapy has been successful in treating some types of leukaemia, but not a rare cancer called T-cell leukaemia. People with advanced disease often do not have enough healthy T cells to generate a bespoke therapy…To sidestep that problem, Qasim’s team collected T cells from healthy donors and edited three sites in the cells’ genomes. The edits were designed to reduce the chance that the recipient’s immune system would reject the donor cells. The edits also aimed to keep the CAR T cells from destroying each other, and to allow the cells to survive when participants are treated with a cancer drug that can kill the T cells. The trial, which is taking place in the United Kingdom, treated its first participant in 2022…the edited CAR T cells were active in the first three participants that they treated, although one participant subsequently died from an infection.
Beam’s approach is similar, but adds a fourth edit that is intended to extend how long the engineered cells are active.
People should not expect access to these revolutionary therapies any time soon. The FDA commonly takes years to approve new drugs and medical devices, and thousands die awaiting FDA approval of new drugs. For example, at least a hundred thousand people died waiting for the FDA to approve beta blockers. One of the FDA officials involved in delaying their approval was John Nestor. Nestor was notorious for following rules in ways designed to frustrate and inconvenience other people. As the Journal of American Physicians and Surgeons notes:
Nestor had the unique habit of getting into the leftmost lane [on the highway] with his cruise control set at 55 mph, the posted speed limit. He would drive at this speed regardless of what came up behind him. Cars would zoom up close to his rear bumper; drivers would flash their lights and blast their horns,some swerving around him on the right while giving him the finger—none of this fazed Nestor in the least. As he explained it, 55 mph was the law, and he had a right to drive in whichever lane he chose: “Why should I inconvenience myself for someone who wants to speed?”
Nestor followed this rigid mindset in his work at the FDA. He was very good at using agency red tape, and minor risks or side effects of drugs, as an excuse to avoid approving life-saving drugs.
Similarly, the FDA didn’t approve a home test for HIV until 24 years after it first received an application. An FDA advisory committee noted that the test held “the potential to prevent the transmission of more than 4,000 new HIV infections in its first year of use alone.” So thousands of people got infected with AIDS as a result of the FDA’s slowness.
90% of those with cystic fibrosis will get a new lease on life with a new breakthrough drug, assuming the FDA doesn’t block it.
Scientists recently engineered bionic silkworms that spin fibers six times stronger than Kevlar.
Scientists also recently came up with an “inverse vaccine” that has shown it can treat auto-immune diseases in a lab setting, creating hope that doctors will be able to use it to reverse devastating diseases like multiple sclerosis. But the FDA commonly takes years to approve new vaccines, so thousands will die waiting for the vaccine to be approved, even if it is perfected.
In other news, artificial wombs could be coming soon, to prevent premature babies from dying or being permanently disabled due to premature life outside the womb. Doctors are already beginning to do womb transplants. A woman who was previously unable to have children recently received her sister’s womb in the first womb transplant in the United Kingdom.
A new ultrasound therapy could help treat cancer and Alzheimer’s disease and skull implants could fight depression.
Doctors recently did the first robotic liver transplant in America. Robots can fit in small spaces in people’s bodies that a surgeon can’t reach without cutting through living tissue, or doing other collateral damage. Doctors recently used a robot to carry out incredibly complex spinal surgery.
Artificial intelligence is now developing highly-effective antibodies to fight disease. Doctors overseas are using artificial intelligence to detect cases of breast cancer more effectively.
Scientists recently developed a treatment for alcoholism that reduces drinking by 90% among lab monkeys.
