Jin Lei Bowen from Oufei Temple
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After 6 years, the name "Han Chunyu" once again jumped into the public eye.
Six years ago (2016), he landed at Nature Biotechnology with a genetic "new scissors" NgAgo.
Due to the extremely high research and commercial value of the technology, it can be described as a rapid popularity:
Nobel Prize-level scholars, more than half of the CNS (abbreviations of the three top journals) articles, opened a new chapter for genome engineering...
However, when it shocked domestic and foreign countries, the voice of "the experiment cannot be reproduced" followed, and many scholars questioned the authenticity of his experiment.
In the end, the incident lasted for three years, and finally ended with the official announcement of "non-subjective fraud" by Hebei University of Science and Technology and the retraction of the Nature sub-journal.
And just recently, a high-scoring paper by a corresponding author named Han Chunyu quietly appeared in Oxford Academic's journal NAR (impact factor 16.971):
The first author of the paper is still the peak of Hebei University of Science and Technology (he also served as a first author in the famous NgAgo paper 6 years ago).
Therefore, under such a "background", Han Chunyu's new research quickly aroused great attention:
Although the main content of the paper does not have much to do with the previous controversy — it proposes a new RNA tracking technology.
But with the previous experience of "experiments cannot be repeated", the new research still seems to be unable to escape the shadow of this hot word.
So what did Han Chunyu's research after six years specifically say?
Six years after the new study
As can be seen from the abstract of the paper, the team proposes a new RNA tracking platform with high sensitivity and specificity.
RNA tracking is a very important part of biomedical experiments, and scientists often analyze multiple life processes in living cells by tracking the trajectory of RNA activity or looking at the distribution of RNA.
Before tracking, the first thing to do is to "light up" the target RNA, that is, let some special molecules bind to the RNA to fluoresce.
However, both the widely used MS2-MCP technology and the Cas9/Cas13 platform have high background noise problems.
Han Chunyu's team mentioned in the paper that the RNA tracking platform they designed can "detect target RNA with almost no background noise."
This is a Cas-based RNA tracking platform: Cas6FC.
Cas6 is a nuclease discovered in 2008 that protects cells from invasion, with RNA binding and shearing capabilities.
Han's team noticed that Cas6 produces structural changes when it binds to cas6 binding sites (CBS) on RNA.
Therefore, based on this feature, they first mutated the key residues of E. coli Cas6 (EcCas6) to obtain dEcCas6 with only RNA binding ability:
Then, the split fluorescent protein fragments (Split Venus) were fused at the N and C ends of the EcCas6 protein to obtain a new chimeric tracer protein: VN-dEcCas6-NC.
When VN-dEcCas6-NC specifically binds to CBS, conformational rearrangement occurs in dEcCas6 and fluorescence is released:
In subsequent experiments, Han Chunyu's team proved that Cas6FC is highly sensitive, and only needs to label a reaction element on the target RNA to "turn on" the Cas6FC fluorescence switch, thereby "lighting up" the RNA.
On this experimental result, Han Chunyu said that Cas6FC can solve the difficulty of high background noise faced by RNA tracking before, but also admits that the experiment is "not full":
Due to the limitations of personnel, funds and equipment, some practical experiments have not been completed, and the paper still focuses on the mechanism and principle.
In the process of communicating with China Science News, Han Chunyu also frankly said:
The newly published study is not related to NgAgo, but it is also a new technology development, or tool research invention.
For the previous hot discussion of NgAgo, he also made the latest response:
We've been working on tool development for the last six years, and we've been doing NgAgo-related tools.
Careful netizens actually found that Han Chunyu actually published the core content of the new study on the bioRxiv preprint website in May 2019, without peer discussion.
So the next question is:
What do you think of this new study?
Although Han Chunyu has stated that this research is not related to NgAgo, after all, it has caused such a big shock in the academic community.
So under such a "background" premise, what do people think about the new research published by Han Chunyu this time?
In the view of Zhihu netizen "Root Bird", the publication of this study is "very rare and very valuable":
Han Chunyu has been grilled on the fire in recent years.
Under this pressure, it is not easy to make an article.
As for the study itself, in the view of "Root Bird", the credibility of the study is still relatively high:
This article has been published on BioRxiv since 2019, and now it is also Open Access, open to the public.
But there's no criticism of the core part of the article yet, and it's also been peer-reviewed by a decent journal, meaning at least more than half of reviewers and editors approve of the article.
As a master's degree, "Bowen", a netizen who had experience in developing RNA imaging tools with CRISPR, also expressed his views on Han Chunyu's new research.
He argues that:
The biggest highlight of this paper is that it uses the protein conformation changes that occur after EcCas6 binds to CBS (Cas6 Binding Site) to control the background signal, resulting in a high signal-to-noise ratio.
However, Bowen also objectively commented:
As far as the data of this paper body is concerned, the signal-to-noise ratio is actually not very high, and the emergence of this tool has not brought about a revolutionary breakthrough, but only the icing on the cake.
That's why it didn't reach top issues like NBT or Nature Methods.
But also based on Han Chunyu's previous experience, Bowen believes that "it is difficult for people in the industry to look at this article without wearing colored glasses":
To make others not wear colored glasses, you can only wait until other research groups repeat the experimental results.
About the "Han Chunyu Incident"
Finally, let's review the "Han Chunyu Incident" that shocked the academic community that year.
The time also needs to go back to May 2, 2016.
On this day, Nature Biotechnology published a study by Han Chunyu called DNA-guided genome editing using the Natronobacterium gregoryi Argonaute.
To put it simply, Han Chunyu's research falls into the category of "genome editing", which is mainly to artificially adjust, change, insert, remove and modify the genome sequence of an individual or species.
The most immediate impact of this technology is the ability to treat previously untreatable diseases, such as genetic diseases.
In this process, the most important link may be the "gene scissors" that can change the "code" of the underlying gene.
Before Han Chunyu, the best in this regard should be CRISPR-Cas9, which was jointly led by Chinese scientist Zhang Feng and American and French scientists.
The "new scissors" proposed by Han Chunyu, called NgAgo, can also effectively cut the target gene.
In this way, if NgAgo can obtain a patent, it is likely to break the monopoly of international gene editing technology.
As a result, Han Chunyu and this paper quickly became popular from the beginning.
However, on May 27, things began to reverse by three hundred and sixty degrees.
One of the most immediate problems is that the experiment cannot be repeated.
The skepticism was first raised at the MIT BBS forum, and on July 29, even by academics at the Australian National University, who had previously announced that the experiment could be repeated.
Successively, scientists from the United States, Spain and other countries have also publicly stated that "it is impossible to repeat the genome editing results of the NgAgo system."
To this end, Nature Biotechnology also published a report on its website on August 8 detailing the controversy of scientists in many countries about this research.
In addition to foreign scholars, domestic scholars also issued questions, on October 10, 13 well-known domestic research scholars real names disclosed the results of "the experiment can not be repeatedly successful".
But the next day, Han Chunyu stood up and explained:
Others can't repeat it, and cell contamination is the most likely.
Even so, the voice of doubt is still fermenting...
Finally, more than a year later, on August 3, 2017, Nature Biotechnology issued a statement retracting Han Chunyu's original publication of the study.
However, according to the description of the surging news at the time, the withdrawal of the paper was proposed by Han Chunyu.
Hebei University of Science and Technology also gave the official survey results on the evening of August 31, 2018:
No subjective fraud was found in Han Chunyu's team.
The retracted paper no longer has the basis for republishment, and the relevant parties have cancelled the honorary titles won by Han Chunyu in accordance with the regulations, terminated the scientific research projects undertaken by Han Chunyu's team and recovered the scientific research funds, and recovered the scientific research performance awards won by Han Chunyu's team.
……
So what do you think about Han Chunyu's new research?