DNA-editing breakthrough could fix 'broken genes' in the brain, delay ageing and cure incurable diseases

DNA-editing breakthrough could fix 'broken genes' in the brain, delay ageing and cure incurable diseases

‘The possible applications of this discovery are vast,’ scientist says

Ian Johnston Science Correspondent November 16, 2016 9 hours ago

Scientists have discovered a new way to edit DNA that could fix “broken genes” in the brain, cure previously incurable diseases and potentially even extend the human lifespan.

The breakthrough – described as a “holy grail” of genetics – was used to partially restore the sight of rats blinded by a condition which also affects humans.

Previously researchers were not able to make changes to DNA in eye, brain, heart and liver tissues.

But the new technique allows them to do this for the first time and could also lead to new treatments for a range of diseases associated with the ageing process.

One of the researchers, Professor Juan Carlos Izpisua Belmonte, said: “We are very excited by the technology we discovered because it’s something that could not be done before.

“The possible applications of this discovery are vast.”

The cells in most of the tissues of an adult body do not divide, making it harder for scientists to introduce changes to the DNA.

But Professor Izpisua Belmonte, of the Salk Institute in the US, said: “For the first time, we can enter into cells that do not divide and modify the DNA at will.”

“We now have a technology that allows us to modify the DNA of non-dividing cells, to fix broken genes in the brain, heart and liver.”

“It allows us for the first time to be able to dream of curing diseases that we couldn’t before, which is exciting.”

The researchers used the technique on rats born with a genetic disease called retinitis pigmentosa, which affects about one in 4,000 people in the UK.

By altering the genes affecting the eyes, they were able to give the rats a degree of vision.

“It should be noted, however, that although tests demonstrated improved visual responses after subretinal injection of [the DNA repair] to three-week-old … rats, the rescue was only partial and not enough to completely restore vision,” the researchers wrote in a paper about their research in the journal Nature.

The technique, known as HITI, was based on the famous CRISPR gene-editing technique.

“The ability to use HITI for in vivo [in a living animal] targeted transgene insertion into post-mitotic [non-dividing] neurons is unprecedented and will help advance basic and translational neuroscience research,” the paper added.

Scientists who were not involved in the study hailed the breakthrough.

Professor Robert MacLaren, of Oxford University, described the research as a “significant advance”.

“Researchers are now using this mechanism to correct gene defects. Clinical trials are a long way off because the CRISPR proteins may cut DNA at other sites that may have untoward effects,” he said.

“Nevertheless, since ageing is defined as picking up DNA mutations, the ability to correct these mutations may in future provide us with a means of extending our lifespan as well as treating many diseases that relate to ageing.”

Dr Andrew Wood, of the Institute of Genetics & Molecular Medicine at Edinburgh University, was similarly impressed.

“This study is a really exciting development for therapeutic applications of genome editing,” he said.

“Although other groups have applied similar approaches in dividing cells grown in the laboratory, this is the first time that it has been used in non-dividing cells in a living animal.

“Before it can be applied to humans, it is now important to improve the efficiency with which the genome editing molecules can be delivered to the relevant cells.”

And Dr Helen O’Neill, of the Embryology, IVF and Reproductive Genetics Group at University College London, said the technique could enable doctors in the future to use gene editing to treat patients.

“This is an elegant study which establishes new means for targeted integration of DNA in cells which are no longer dividing,” she said.

“These cells have long been considered a hurdle in somatic cell therapy.

“Further work will need to be done on improving efficiencies, but this work certainly shows new avenues for alternative research into gene therapies.”

Professor Robin Lovell-Badge, of The Francis Crick Institute and one of the UK’s leading geneticists, said: “As reported, the methods are not super-efficient. For some genetic diseases it is not necessary to target all cells within the affected tissue, but levels of five per cent or so would only give marginal benefit.

“However, with improvements in this type of technology, which seem inevitable these days, it is likely that the methods developed here could prove to be a very useful way of adding genes to non-diving cells, certainly for purposes of basic research, and perhaps eventually for gene therapy to treat otherwise incurable diseases.

“It is a complicated paper, and it does not quite reach the level as hyped in the press release, but it is indeed rather important.”


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