Scientists at MIT and Harvard have discovered two gene editing techniques to fix mutations that cause diseases like cystic fibrosis and Duchenne muscular dystrophy.
Both diseases, and about half all human genetic disorders, are caused by mutations in single letters in the human genome, in which an ‘A’ appears where there should be a ‘B.’
The newly-developed gene editing systems can target the smallest units of our DNA or RNA to undo the mutation that causes cystic fibrosis.
One system edits DNA in the genome itself, while the other targets RNA, which transports genetic messages for making proteins.
The editing systems work in living cells, and if researchers can find ways to deliver them to human patients safely and effectively, they could be used to reverse the mutations that cause more than 15,000 genetic diseases.
Both DNA and RNA contain four base components: adenine, thymine, guanine and cytosine.
Cystic fibrosis is caused by an inherited genetic mutation that leads to abnormal mucus production in the lungs and digestive system. The thicker-than-normal mucus builds up in and blocks airways.
The disease is rare, affecting about 200,000 people in the US each year. It can be managed with breathing machines, inhalers and medications, but some affected by it will eventually need lung transplants. There is no cure for cystic fibrosis and it can be fatal.
Cystic fibrosis could be prevented or corrected if only there were a ‘G’ in the genome where the disease’s victims have an ‘A.’
With the new gene editing technologies from the Broad Institute of MIT and Harvard, scientists could rewrite the part of the genome or its messenger that spells cystic fibrosis.
The research group that created a DNA base editor, led by Dr David Liu, are calling their breakthrough a ‘molecular machine.’ Their gene editing system is technically called the Adenine Base Editor, or ABE.
The ‘A’ in ABE is for ‘adenine,’ one of four chemical bases that are the smallest elements of our genomes. Adenine is always paired with thymine, and guanine is always paired with cytosine.
The order and repetitions of three billion of these pairs – AT and GC – throughout the genome code for everything about us. But, the simplicity of the system means that one wrong letter can throw off important parts of us.
ABE targets the ‘A,’ adenine, and rearranges its atoms to turn it into guanine. So, where there is an incorrect AT set of base pairs in the genome, ABE can reset it to a GC.
Dr Liu and his lab has already created BE4, a second and improved version of its base editor for turning GC base pairs into AT base pairs.
Together, these genetic editors give scientists the remarkable ability to rewrite any mutated base pair in the genome.
The gene editors are developments on the CRISPR technology which allows scientists to more efficiently target and edit the genome, developed by Dr Feng Zheng and his lab at the Broad Institute.
CRISPR works but making cuts in the genome, and Dr Zheng’s latest technique, REPAIR is essentially the same thing, but for RNA.
RNA editing avoids interfering with the genome itself. Because RNA plays a communication role in humans, rather than being the fundamental genetic information itself, changes to it might be more flexible, and reversible.
However, RNA degrades over time, so the impermanence of changes to its component parts (called nucleoside bases) could be disadvantageous too.
Dr Zheng and his lab used their REPAIR system to correct a mutation that causes a form of anemia.
Dr Liu’s team successfully used ABE in live human cells to correct a mutation that causes the body to retain more iron from our diet than it should.
While the study authors acknowledge that ABE is an exciting piece of the puzzle, it, like other CRISPR-derived technologies are a long way from ready to use in medical care.
‘Creating a machine that makes the genetic change you need to treat a disease is an important step forward, but it’s only one part of what’s needed to treat a patient,’ Dr Liu said in a press release.
‘We still have to deliver that machine, we have to test its safety, we have to assess its beneficial effects in animals and patients and weigh them against any side effects – we need to do many more things,’ he says.
If the technology could prevent or reduce the mutation that causes cystic fibrosis, the disease would be stopped in its tracks, and not passed on to future generations.
Daily Mail
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