CRISPR-Cas9 is a technology that allows scientists to essentially cut and paste DNA; raising hopes for genetic fixes for disease. However, there are concerns about its safety and ethics.
The technology that produced a global scandal in China last year has entered into clinical trials to treat sickle cell anaemia and eye disease.
Researchers in the US have begun editing the genes of adults with devastating diseases, using a tool known as CRISPR (which stands for clustered regularly interspaced short palindromic repeats). China has already launched multiple trials of CRISPR in humans. Last year, Chinese researcher, He Jiankui, caused a global outcry when he used the same tool to gene edit twin baby girls when they were just embryos. There is far less concern about other CRISPR trials either in the US or China, in part, because genetic changes in the adults treated will not be passed on to future generations. “If it’s done well and carefully, I’m not so worried, to be honest,” said Robin Lovell-Badge, a British geneticist and stem cell scientist, regarding the use of CRISPR in these new trials.
When Chinese scientist He Jiankui announced that he’d gene-edited twin baby girls to remove a gene that would prevent them from getting HIV, the virus carried by their father, it shook the world.
His work was described as disturbing and clandestine. He was called China’s Frankenstein and stupendously immoral. By eliminating their chances of contracting HIV, he opened the girls up to susceptibility to other diseases. And HIV can be treated, so it’s not seen as the right issue to target. Plus, the experiment wasn’t sanctioned by the international scientific community, which wanted human gene editing to progress cautiously.
The core issue is whether such gene editing would cross an ethical red line because it would pass on that change to future generations, and ultimately alter the human species. Regulations arguably prohibit it in many countries, China included, but some of the languages in those laws is soft.
Early this year, Kulkarni’s company, in collaboration with Vertex Pharmaceutical began testing CRISPR gene editing on patients with sickle cell disease and beta-thalassemia. Researchers are editing genes in blood cells removed from each patient and then replacing them to restore normal haemoglobin, which transports oxygen throughout the body.
In late July, pharmaceutical giant, Allergan, and genome editing company, Editas Medicine, announced that they were ready to enrol subjects in a clinical trial to treat one of the most common inherited forms of childhood blindness, called Leber Congenital Amaurosis Type 10. The companies claim that trial is the first to use CRISPR to edit genes inside the body. The eye is considered a relatively safe place to test the technology because changes made there should not affect other areas.
The core issue is whether gene editing would cross an ethical red line because it would pass on that change to future generations, and ultimately alter the human species
The gene edits made by Vertex and CRISPR Therapeutics will suppress a gene called BCL11A, which will restart production of fetal haemoglobin, a type of haemoglobin that helps fetal blood hold onto oxygen. Even people who inherit the sickle cell gene from both parents make fetal blood (or they would not have survived to birth), so reactivating fetal haemoglobin should allow them to lead normal, healthy lives.
Those edits are made on blood cells that have been removed from the body and are then reinserted after the patient has undergone a procedure to clear out diseased blood precursor cells. The gene editing is transient, and the edited blood cells undergo quality checks before being reinserted, minimising the risks of unintended gene edits.
The edited cells then grow into the bone marrow and begin making healthy red blood cells that do not sickle, so they will not stick to the inside of blood vessels, cutting off circulation and causing dangerous pain crises. People born with sickle cell and a genetic fluke that allows them to keep making fetal haemoglobin do not suffer from the disease, research showed. And sickle cell does not recur in patients who get bone marrow transplants that allow them to make healthy blood cells, which is currently the only way to cure the disease but is available to only a small minority of people.
Recherché said this result gave him confidence that the gene edits can potentially provide meaningful and lifelong benefits to patients.
CRISPR will be used inside of the body to treat inherited blindness.
Patients in the US are about to be the first enrolled in a gene-editing technique, used inside the body to help treat them of a specific inherited form of blindness.
People with this disease have regular eyes but are missing a gene that allows light to be converted into signals sent to the brain, and which allows them to see.
The disease is called Leber Congenital Amaurosis and those who will be taking part in the blindness study have one form of it.
It is the most common cause for blindness inherited in children, occurring in around two to three out of every 100,000 births.
The experimental study will involve both children and adults in the treatment, to restore vision in their eyes.
CRISPR will edit the gene that these patients lack to see, by cutting and editing DNA in a specific place. It’s meant as a one-time operation, which alters the person’s DNA forever.
The researchers said they were still confident that gene editing would be medically useful.
Professor Vinit Mahajan of Stanford University also took part in the research. He said, “We’re still upbeat about CRISPR. We are physicians, and we know that every new therapy has some potential side-effects but we need to be aware of what they are.”
The writer is a retired official of Govt of Sindh Health Department