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New advance in DNA base editing tools

30 October 2017

By Julianna Photopoulos

Appeared in BioNews 924

Scientists have further developed the genome editing technique known as 'base editing' to turn adenine-thymine base pairs back to guanine-cytosine.

They hope the approach could one day be used to treat diseases associated with single genetic mutations.

'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.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

11 December 2017 - by Isobel Steer 
Scientists in California have used a modified form of the CRISPR/Cas9 genome editing approach to epigenetically treat diabetes, kidney disease and muscular dystrophy in mice...
20 November 2017 - by Helen Robertson 
For the first time ever, researchers have been able to film, in real-time, the activity of the CRISPR technique on a strand of DNA...

02 October 2017 - by Dr Rachel Brown 
A genome editing technique called 'base editing' has been used to correct the mutation causing the inherited blood disorder beta-thalassemia in human embryos...
02 October 2017 - by Sandy Starr 
What do patients and laypeople think and know about genome editing and its implications? What are the best ways for experts and others to discuss genome editing in public, so as to improve public understanding and avoid confusion? The Progress Educational Trust has set out to answer these questions, with its 'Basic Understanding of Genome Editing' project....
14 August 2017 - by Emma Lamb and Annabel Slater 
Scientists have repurposed CRISPR to target the repetitive RNA sequences responsible for several genetic diseases...

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Published by the Progress Educational Trust

CROSSING FRONTIERS

Public Conference
London
8 December 2017

Speakers include

Professor Azim Surani

Professor Magdalena Zernicka-Goetz

Professor Robin Lovell-Badge

Sally Cheshire

Professor Guido Pennings

Katherine Littler

Professor Allan Pacey

Dr Sue Avery

Professor Richard Anderson

Dr Elizabeth Garner

Dr Andy Greenfield

Dr Anna Smajdor

Dr Henry Malter

Vivienne Parry

Dr Helen O'Neill

Dr César Palacios-González

Philippa Taylor

Fiona Fox

Sarah Norcross

Sandy Starr


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