New NgAgo protocol: helpful or more of a red flag?

The supposed new gene editing technology NgAgo has had the scissors taken to it with basically no one able to get it to work conclusively and now the professor who led the work, Chunyu Han, has posted a new NgAgo protocol on the Addgene website.

The new NgAgo protocol is really more of an abbreviated methods description with just a few new hints at getting it to work such as testing your cells for mycoplasma.

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Controversy over CRISPR challenger NgAgo irreproducibility reported

Does the new gene editing method NgAgo work or not? If not, what happened? The answers to both questions seem to depend on who you ask and what you read.

Fang Shimin (方是民) NgAgo

Wikipedia image

As much as CRISPR has been the revolutionary in the genetic modification technology arena over past methods, could CRISPR itself in the next few years become obsolete having been replaced by other new technologies such as the upstart NgAgo? I doubt it.

The odds for NgAgo making a run in this field may have gone down lately, at least based on a comment left by Sheng Qiang on my original post on NgAgo:

“A war of word broke out on the reproducibility of Han’s work these days, especially on the Mitbbs website. The doubters, represented by Zhouzi Fang, said that no labs have repeated Han’s work, especially the Figure 4 results. The supporters claimed that 20 labs in China already repeated Han’s work, yet no data have been shown to support the claim. The doubters suspect that this is another STAP cell incident for China. To be fair, we should probably give more time for labs around the world to repeat Han’s work, which was trumpeted in the Chinese media to be a Nobel prize worthy scientific breakthrough. Let’s just hope that this will not go down the same path as the STAP cells.”

The Zhouzi Fang mentioned seems to most likely be Fang Shimin (方是民), pictured above, who has a Wikipedia page here that mentions his role as a popular science writer who campaigns against pseudoscience and fraud. It also discusses a number of controversies in which he has been involved. I wonder if he might be like Japan’s juuichijigen who played a key role in uncovering STAP. I don’t know.

I’m hoping to learn more about this NgAgo situation so that we all can better judge what the status of NgAgo research might be. The notion that this could be another STAP-like situation would be very unfortunate, but it seems there’s not enough information now to judge and that’s a serious thing to assert. I agree with the commenter that more time is needed before we can be sure what’s what here.

So what is out there on discussions over NgAgo as to whether it works or not?

I did find this page on an “NgAgo” search onMitbbs (which when Google crudely translates it) seems to fit with what the commenter says about a war of words, but I have no idea if that page is reliable.

I also found this Chinese-language science news site reporting on the NgAgo controversy.

This Google group page on NgAgo also has some researchers reporting it doesn’t work for them, but others said it did work.

Overall, I’d say the jury is out, but it’s clear there are strong opinions both ways on NgAgo.

NgAgo a-go-go: top 5 bullet points on upstart CRISPR challenger

NgAgoThe gene editing technology CRISPR has been arguably the top story in the biomedical world in the last two years, but going forward there is a CRISPR challenger in upstart gene editing technology NgAgo.

For more background on NgAgo and the key first published paper on its genetic modification characteristics see my post here. 

In the comments on that post and in discussions I’ve had with other researchers, some key points have crystalized on NgAgo versus CRISPR at this time. As a possible CRISPR challenger, how does NgAgo fare?

Broader possible applicability. The lack of a PAM site requirement for NgAgo means it is almost certain that for some specific gene editing applications, NgAgo will work and CRISPR won’t. Design of NgAgo guides seems to be a simpler matter too because no PAM is needed (more on guides below). In that first NgAgo paper they reported effective editing of 8 different genes with good efficiency so it’s unlikely there is a strongly required DNA sequence context needed for NgAgo. However, it is still formally possible that NgAgo in some contexts will have some kind of preference for certain DNA sequences.  Further study will help resolve this more concretely, but so far this is looking like a major plus for NgAgo.

DNA guides should be a lot easier. The use of DNA-based guides will make gene editing easier as opposed to RNA-based guides. At the very least you eliminate a cloning step and you can just order oligos, which you can phosphorylate in your lab to use as guides by transfection.

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Will new gene editing tech NgAgo challenge CRISPR?

What could be better than CRISPR for gene editing?

A new genetic modification technology called NgAgo has some researchers really excited. How does it compare to CRISPR?

I’ll admit it that as a scientist who works on genetics and genomics, I am really enjoying the power and simplicity of CRISPR-Cas9 type technology for genome editing. We are working with it extensively in my lab. One of the remarkable things about CRISPR is how fast the technology has evolved in just the last 2 years.

NgAgo

NgAgo, Figure 5, Nature Biotechnology

Despite all that warp speed for CRISPR, some are asking: could NgAgo zoom past CRISPR?

While NgAgo is indeed a nifty new genome editing technology based on DNA guides instead of RNA guides, it’s not going to immediately race ahead of CRISPR…not yet any way. Still it’s got people buzzing.

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