‘Ambitious, impossible’: controversy over Chinese scientist He Jiankui’s latest research plan targeting muscular dystrophy

But his visa was revoked late Tuesday night after immigration officials said they suspected he lied on his application form and another criminal investigation would be launched. It’s not clear what impact the pending investigation will have on He’s research.

“The news will increase my confidence in Dr. He said, “I’m sure he wouldn’t do anything illegal.”

Li is the organizer of a DMD patient group. His son was diagnosed with the disease in 2018. DMD is caused by a genetic problem in the production of dystrophin, a protein in muscles. It occurs in 1 in 3,500 to 5,000 newborns.

There is no cure for DMD, but some medications and therapies can slow its progression and improve patients’ quality of life. Over the past decade, the United States and Japan have approved several drugs to treat some types of DMD caused by a specific mutation. Only a small percentage of patients with DMD can be treated, and no drug has been introduced in China.

“I have dr. Contacted He because he had already successfully performed genome editing on embryos in 2018. He confirmed that it was successful,” Li said. “If he can help us develop a drug, I am sure all our children can be cured in a short time.”

He was heavily criticized by the scientific community after announcing in 2018 that he had created two genetically engineered twin girls try to make them resistant to HIV. A third child was born the following year.

He was arrested and sentenced to three years in prison and fined 3 million yuan in 2019 for “illegal medical practices.” He was released from prison in April last year.

A number of pharmaceutical companies are developing drugs and therapies to treat DMD. Li asked He if he could develop a more advanced cure to treat or even cure the disease.

“Professor He’s answer was very clear. He said theoretically it’s possible to cure the disease,” Li said, adding that he promised he could “absolutely guarantee” children under the age of three would be cured.

He told the Post earlier this month that he wants to use gene-editing technology to treat diseases and that the technology could be the perfect solution for rare genetic diseases “because most rare diseases are genetic diseases that are caused by genetic mutations caused”.

“If we can fix the genes through genome editing, we can cure rare diseases,” he said.

Researchers are testing two gene therapy approaches to treat DMD – gene transfer and gene editing. Gene transfer delivers a functional version of the defective gene into cells that can produce dystrophin, an important muscle-building protein that is largely absent in people with DMD. Gene editing, on the other hand, aims to correct the defective gene by making DNA.

A number of DMD gene transfer studies are in clinical trials, and research is being done in animals on how to gene edit the disease.

He said one innovation he plans to incorporate into the research is the development of a viral vector called an adeno-associated virus (AAV) vector, which would function as a vehicle to deliver gene-editing tools directly into a cell.

Because muscles make up up to 40 percent of total body mass, it would take high doses of the virus to reach muscles. However, the viruses often ended up in the liver or other organs and tissues, which could cause serious safety problems.

He said he wants to use artificial intelligence techniques to directly advance AAV to specifically target muscle cells so that less virus can be used, making experiments safer.

“Using viral vectors in large doses is the biggest risk of genome editing and gene therapy,” he said, adding that he plans to develop a viral vector in six months and start human clinical trials in about two years.

“I think we can do it,” he said. “It’s a small step on the shoulders of giants. The previous giants have done well in gene editing for DMD. What we need is the development of a viral vector.”

Researchers in the US – at MIT and Harvard’s Broad Institute and Harvard University – have developed a group of new viral vectors that they say “reach muscles more than 10 times more efficiently than those currently used in clinical trials and largely avoid the.” Liver”.

According to the Broad Institute’s website, the vectors could be used to deliver therapeutic genes at doses about 100 to 250 times lower than other viral vectors used in other studies. Their study was published in Cell in September 2021.

The study’s lead author, Broad researcher Sharif Tabebordbar, said the results were the result of 10 years of work.

Robin Lovell-Badge, head of the Stem Cell Biology and Developmental Genetics Laboratory at the Francis Crick Institute in London, said that if he had just started his research, “there is absolutely no way he’s going to get a clinical trial in two years’ time.”

“He has to have the results of all these experiments first — the human cell lines, animal models, toxicity tests,” Lovell-Badge said. “He hasn’t even gotten to the stage where he has a viral vector that he’s happy with.

“It takes a long time because it has to be done very carefully. You cannot rush these things because if you get it wrong, people will suffer or die from the “treatment” rather than the disease. Not only does it set back what he’s doing, but the field, because that’s when people get really nervous about volunteering for a clinical trial.

“So I get very nervous when he says he’s going to start a clinical trial in two years.”

Lovell-Badge said he was a little surprised he was allowed to do any research, particularly with patients, given what he did in 2018.

Eben Kirksey, a medical anthropologist at Oxford University, said responsible clinical research is very carefully formulated so patients don’t have unrealistic hopes of a new application or a new therapy.

“The likelihood that a phase 1 clinical trial will bring dramatic benefits to patients is quite low, but there is real risk to patients and those risks could include death, as has been the case with recent events.” said Kirksey. “They could also include a wide range of other serious adverse events.”

Events Kirksey was referring to included the death of Terry Horgan, a 27-year-old with DMD, who died in October while participating in a clinical trial. Horgan was the sole participant in a phase 1 study evaluating the effects of gene-editing therapy to treat DMD.

“In general, it takes many years, sometimes even decades, to go from pre-clinical work to early clinical trials to a therapy that has actually shown benefits for patients,” Kirksey said. “I think a broad societal hazard in his current line of research just relates to external hopes that are inconsistent with the current state of the art.”

Joy Zhang, a sociologist at the University of Kent in Canterbury, England, said one of her concerns is that China has not provided clarity on whether it would be restricted in conducting any type of research involving human subjects and what regulatory protections are in place be .

“There is no way for DMD patients in China and abroad to verify whether He’s research is legitimate, how it’s regulated and evaluated,” she said.

“The decision to cure a rare disease may seem noble. But given his history of exploiting the desperation of socially or medically marginalized groups and tricking them into seeking unnecessary medical treatment, I am concerned that his focus on DMD is part of a repeating pattern.”

He said the experiments were being conducted to the highest international standards. They would use rodent models and human stem cells, and then do toxicity tests in monkeys, and an international scientific committee and ethics committee would review the data.

He said he plans to do genome editing on somatic cells from young, non-reproductive cells that would not be passed on to the next generation. He said he believes that in the next 10 years, most rare diseases could be treated through genome editing.

Gang Bao, a bioengineer at Rice University in the US, said He’s two-year research plan is “very ambitious”.

Bao’s team uses gene-editing technology to treat sickle cell anemia, an inherited disease caused by a genetic mutation. He said there are many challenges in genome editing for rare diseases.

Aside from off-target effects, his team found that CRISPR-Cas 9 genome editing can induce large gene changes such as deletions and insertions at the target site, and the unintended modifications can persist.

“It’s very complicated,” Bao said. “That’s why I think he’s very ambitious.”

When asked if he was worried about He’s DMD research given the criticism of his experiment in 2018, Li replied, “When you’re at your hungriest, do you still decide whether you want to eat meat or buns?”

Li said He’s research data should be approved by the scientific and ethics committees, and the drug’s safety and toxicity should be tested before it’s used in humans.

“We really want to have medicines, but our children also have to stay alive,” he said.