30 October 2017
ByAppeared in BioNews 924
'We are currently using base editing to try to study or validate potential future therapeutic treatments for blood diseases, genetic deafness, genetic blindness … and some neurological disorders as well,' said author Professor David Liu of Harvard University to The Guardian.
Unlike the more common CRISPR/ Cas9 technology, base editing does not cleave DNA to make edits, reducing the substantial number of errors at target sites such as random insertions or deletions. Yet until now, this technique - developed last year by the same team - only allowed the conversion of guanine-cytosine (G-C) into adenine-thymine (A-T).
'This class of mutation, changing a G-C to an A-T, accounts for about half of the 32,000 known pathogenic point mutations in humans,' Professor Liu told Wired.
The new approach uses an enzyme that changes adenine into a molecule called inosine. Another enzyme, Cas9, then places a 'nick' in the strand across from the inosine, which stimulates the cell's machinery to begin a repair.
'That nick prompts the cell to replace the T with a C, because the base opposite the T has been converted to inosine, which pairs with C,' said Professor Liu.
The process worked in both bacteria and human cells.
'It's a very elegant study,' Dr Andrew Bassett, head of research in cellular operations at the Wellcome Trust Sanger Institute, told The Scientist. 'Being able to extend [base editing] to other types is really quite important.'
Dr Helen O'Neill from University College London, who was not involved in the research, said: 'The ability to now directly alter all four base-pairs with such specificity adds more ammunition to the genome editing artillery and will be incredibly powerful in the research of diseases and future restoration of disease-causing mutations.'
But according to The Guardian, Professor Liu warns that more work will be needed to cure diseases. 'There are many additional steps beyond simply making the mutation that may be needed to treat [a] disease,' he said.
Professor Darren Griffin of the University of Kent, who was not involved in the research, commented that as the team corrected a genetic defect in a human cell line, 'questions are bound to be asked about gene editing in an IVF setting.' However, he added that in addition to the ethical arguments, 'there are many practical hurdles that mean that the greatest benefit of the technology might well be as a research tool.'
The study was published in Nature. Another study, published in Science, reveals additional exciting achievements in genome editing techniques: adenine turned into inosine in RNA (also in BioNews 924 this week).
The latest developments in genome editing will be discussed at the session 'What Next for Genome Editing? Politics and the Public', at the Progress Educational Trust's upcoming public conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction'.
The conference is taking place in London on Friday 8 December 2017. Full details - including sessions, speakers and how to book your place - can be found here.