When Li Zhaoxia, the father of a nine-year-old boy with muscular dystrophy, contacted controversial biophysicist He Jiankui last year to ask whether He could help to develop a drug to treat the disease, He replied he first needed to learn about it. Two months later, He told Li that, technically speaking, he was “capable of curing the disease”. He released his research plan on Twitter in December, aiming to raise 50 million yuan (US$7.3 million) for Duchenne muscular dystrophy (DMD) research and to start clinical trials in March 2025. DMD is a rare genetic disease that mostly affects boys and is characterised by progressive muscle damage. Some scientists have said He could not possibly finish preclinical research in just two years. He applied for a visa through Hong Kong’s Top Talent Pass Scheme earlier this month and it was approved in about a week. He was in contact with universities and research institutions in Hong Kong and planned to conduct research on gene therapy for rare diseases. But his visa was revoked late on Tuesday night after immigration officials said they suspected He had lied on his application form and a follow-up criminal investigation would be conducted. It is not clear what impact the pending investigation will have on He’s research. “The news will not affect my confidence in Dr He,” Li said. “I’m sure he wouldn’t do anything illegal.” Li is the organiser of a DMD patient group. His son was diagnosed with the disease in 2018. DMD is caused by a genetic problem in producing dystrophin, a protein in the muscles. It occurs in one 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 to China. Chinese scientists say new cell editor could speed up genetic disease therapy “I contacted Dr He because he successfully performed genome editing in embryos back in 2018. He verified that it was successful,” Li said. “If he can help us to develop a medicine, I’m sure all of our children can be cured in a short time.” He was heavily criticised by the scientific community after he announced in 2018 that he had created two genetically modified twin girls to try to make them resistant to HIV. A third child was born the following year. He was detained and sentenced to three years in prison and fined 3 million yuan in 2019 for conducting “illegal medical practices”. He was released from jail 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 remedy to treat or even cure the disease. “Professor He’s reply was very clear. He said in theory, it was fully achievable to cure the disease,” Li said, adding that He had promised he could “absolutely guarantee” that children under three years old would be cured. His son’s rare disease turned this Chinese father into a home-grown drug-maker He told the Post earlier this month that he wanted to use gene-editing technology to treat disease, and the technology could be the perfect solution for rare genetic diseases, “because most rare diseases are genetic diseases, caused by genetic mutations”. “If we can repair the genes using 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 inside the cells, which can produce dystrophin, an important muscle-building protein that is largely absent in people with DMD. Gene editing, meanwhile, aims to correct the defective gene by making DNA. A number of DMD gene transfer studies are in clinical trials and research on gene editing for the disease is being conducted on animals. He said one innovation he wanted to involve in the research was to evolve a viral vector called an adeno-associated virus (AAV) vector, which would work like a vehicle to deliver gene editing tools directly into a cell. Because muscle comprises up to 40 per cent of total body mass, high doses of the virus would be needed to reach the muscles. However, the viruses often ended up in the liver or other organs and tissues, which could cause serious safety problems. He said he wanted to use artificial intelligence techniques to directly evolve AAV to make it specifically target muscle cells, so that less of the virus could be used, making experiments safer. “The use of viral vectors in large doses is the biggest risk of genome editing and gene therapy,” He said, adding that he planned 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 on gene editing for DMD. What we need is to evolve a viral vector.” Researchers in the US – at the Broad Institute of MIT and Harvard, and Harvard University – have developed a group of new viral vectors that they say is “more than 10 times more efficient at reaching muscle than those currently used in clinical trials and largely avoids the liver”. China tightens rules on genetic research after designer baby scandal The vectors could be used to deliver therapeutic genes at doses around 100 to 250 times lower than other viral vectors used in other studies, according to the Broad Institute’s website. Their study was published in Cell in September 2021. The lead author of the study, Broad research scientist Sharif Tabebordbar, said the findings 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 could get a clinical trial in two years”. “He has to have the result from all those experiments first – the human cell lines, animal models, toxicity tests,” Lovell-Badge said. “He hasn’t even got to the stage of having a viral vector that he’s happy with. “It takes a long time because it has to be done really carefully. You can’t rush these things, because otherwise, if you do it wrong, people suffer or they die from the ‘treatment’ rather than the disease. That sets back not just what he’s doing, but it sets back the field because then people get very nervous about volunteering for a clinical trial. “So I get very nervous when He says he’s going to start doing a clinical trial in two years.” Lovell-Badge said he was a little surprised that He was allowed to do any research, especially that involving patients, given what he did in 2018. Eben Kirksey, a medical anthropologist at the University of Oxford, said responsible clinical research was very carefully worded so that patients did not have unrealistic hopes about a new application or a new therapy. “The probability that a phase 1 clinical trial is going to deliver dramatic benefits to patients is quite low, but there is a real risk to patients and those risks could include death as happened with recent events,” Kirksey said. “They could also include a broad range of other serious adverse events.” The events Kirksey referred to include the death of Terry Horgan, a 27-year-old with DMD, who died in October while taking part in a clinical trial. Horgan was the sole participant in a phase 1 study designed to evaluate the effects of a gene-editing therapy to treat DMD. “Generally it takes many years, sometimes even decades, to move from the preclinical work to the initial clinical trials, to a therapy that actually has demonstrated benefits to patients,” Kirksey said. “I think one broad social risk with his current line of research just relates to outside hopes that aren’t matched with the current state of the technology.” Joy Zhang, a sociologist at the University of Kent in Canterbury, England, said one of her concerns was that China had not provided any clarity on whether He was restricted in conducting any type of research relating to human subjects and what regulatory safeguards were in place. “There is no way for DMD patients both in China and abroad to check if He’s research is legitimate, how it will be regulated and assessed,” she said. Why He Jiankui’s genetic adventurism is bad news for science “The choice of curing a rare disease may appear to be a noble one. But given He’s history of exploiting the desperation of socially or medically marginalised groups, and deceiving them into taking on unnecessary medical treatments, I worry his focus on DMD is part of a repeated pattern.” He said the experiments would be conducted under the highest international standards. They would use rodent models, human stem cells, and then carry out toxicity tests on monkeys, and an international scientific committee and ethics committee would check the data. He said he planned to perform genome editing on boys’ somatic cells, non-reproductive cells that would not passed down to the next generation. He said he believed that in the next 10 years, most rare diseases could be treated by genome editing. Gang Bao, a bioengineer at Rice University in the US, said He’s two-year research plan was “very ambitious”. Bao’s team uses gene-editing technology to treat sickle cell disease, an inherited disease caused by a genetic mutation. He said there were many challenges when performing genome editing for rare diseases. Apart from off-target effects, his team found that CRISPR-Cas 9 genome editing could induce large gene modifications, such as deletions and insertions, at the on-target cut-site, and the unintended modifications might persist. “It’s very complicated,” Bao said. “That’s why in my view He is very ambitious.” Asked whether he worried about He’s DMD research in light of the criticism of his experiment in 2018, Li replied: “When you are at your hungriest time, do you still choose 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 was used in humans. “We are eager to have medicines, but our children also have to stay alive,” he said.