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NgAgo is a no-go

7 August 2017
Appeared in BioNews 912

The original paper promoting a new genome editing technology known as Natronobacterium gregoryi Argonaute (NgAgo) has been retracted.

The retraction follows repeated failures to repeat the results described. Published in Nature Biotechnology in May 2016, the paper created a media sensation in China when it was suggested that NgAgo could supersede the CRISPR/Cas9 genome editing system.

However, the paper quickly drew widespread criticism as scientists began reporting an inability to reproduce the results.

'Despite the efforts of many laboratories, an independent replication of [our] results has not been reported,' the scientists, led by Dr Chunyu Han of Hebei University of Science and Technology, stated in their retraction notice. 'We are therefore retracting our initial report at this time to maintain the integrity of the scientific record.'

NgAgo appeared to show advantages over the CRISPR/Cas9 system - greater guide stability, reduced off-target editing, and the use of reagents that are easier to synthesise and handle.

But scientists who could not reproduce the results using the described protocols soon began citing their concerns over social media, in blogs, and in published papers. In November 2016, Nature Biotechnology published an expression of concern alongside the paper, presenting a collection of data that challenged the original findings.

Dr Han's team and other independent groups responded by coming to the journal with new data supporting the reproducibility of NgAgo genome editing, but could not sufficiently refute the growing amount of research that continued to challenge the original findings.

'Some of us have even sent visiting researchers to [Dr] Han's laboratory but they were not allowed to perform genome editing experiments involving mammalian cells when they were there,' a team of Chinese and US scientists led by Dr Shawn Burgess of the National Human Genome Research Institute reported in November 2016 to the journal Protein & Cell. 'Consequently, none of them returned with any information confirming Han's data.'

An editorial by Nature Biotechnology concluded: 'We are now convinced that the decision of Han and colleagues to retract the paper is the best course of action to support the integrity of the published record.... When it comes to biology, answers are often not definitive. And when it comes to replication studies, the one thing we know is that it takes time. In the case of NgAgo, the time has come and the data have spoken.'

Though the NgAgo controversy has led to the original paper's retraction, Dr Han and his team have not given up on NgAgo, stating in the retraction notice: 'We nevertheless continue to investigate the reasons for this lack of reproducibility with the aim of providing optimised protocol.'

Authors retract controversial NgAgo gene-editing study
Nature News |  3 August 2017
DNA-guided genome editing using the Natronobacterium gregoryi Argonaute - Retraction Notice
Nature Biotechnology |  2 August 2017
NgAgo Paper Retracted
GenomeWeb |  3 August 2017
Scientists Can’t Replicate Gene-Editing Method
The Scientist |  21 November 2016
“The data have spoken:” Controversial NgAgo gene editing study retracted
Retraction Watch |  2 August 2017
Time for the data to speak
Nature Biotechnology |  2 August 2017
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