Are StickyFlares smarter than SmartFlares?

Update (19/08/2015): Dave Mason has posted a detailed critique of this paper at PubPeer

Update (19/10/2015): We have submitted a response to this paper as a Letter to the Editor of PNAS. It is currently available as a preprint.

Update (16/11/2015): Inder Verma, Editor of PNAS, has decided that our letter “does not contribute significantly to the discussion of the StickyFlare paper.”

A quick post before I take off to Boston tomorrow for the American Chemical Society national meeting. I informed Chad Mirkin of my Monday talk where I will discuss the SmartFlares (talk on Monday, abstract). In his reply, he pointed me to a contributed PNAS paper they published in July on StickyFlares (Links: article, Northwestern press release). The questions that this technology raises are the same as the ones raised by the SmartFlares, as discussed in a previous post. Eight years after the initial NanoFlare paper, they are still not answered in this new article.

Check the latest results of our SmartFlare studies on the open notebook and data repository.

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14 comments

  1. Really enjoy reading about the nanoflare work! Enjoy Boston. Noticed that the featured post remains at top of page, makes it difficult for casual checkers to see updates to page with new posts like this.

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    1. Don’t know why I had made that post sticky. That’s sorted. Glad you are enjoying reading about the nanoflare work: expect some more in the coming weeks. You will have maybe noticed the update with a link to a great comment by Dave Mason at PubPeer.

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  2. Thanks for the links lanonymous. I have looked at these and I am happy that others contribute to these discussions… helps with the fatigue indeed (I do not have any urge to add anything).

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  3. Mirkin has loved these application sounding things for a long, long time. And he is very bombastic and personally ambitious. He gives a lively talk, which means a lot. But I wouldn’t do a collaboration or a business deal with him and would counsel students away from associating with him.

    I think the gold DNA nanoparticle is legit and also the nanopen writing. [Funny thing is that he ridiculed the person (Robert Piner, elderly postdoc) and the idea. But Piner right away saw what was going on and the importance of it and pushed it through until Chad got on board…and reaped a lot of the credit.]

    I have some doubts about Chad’s student’s monolayer covered superconductor work, especially the article with McDevitt. Never pursued it to ground, but outsiders and insiders were skeptical of parts of it, which I took as a real warning. Think the research effort ended after work from 1996-2000 (and no in in science is extending it), so any sins here are probably disappeared into time and irrelevance.

    There was also a grad student of his touting a “windshield wiper” coordination compound, that claimed some sort of exchange going on with different parts of the ligand. But it ended up being a symmetry operation (C2 axis or such). That may have gotten caught before publication though…amidst some resistance.

    Anyways…caveat emptor.

    P.s. I have a hard time understanding what the issue is with the nanoflares (what is special about them, what your doubts are, how the other side is digging in). With stripy it was easy to follow, but seems like nanoflare there is no overview or intro. I wasn’t even clear if there is some big disagreement here or not, the writing was so in progress and so mild mannered.

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    1. Thanks for the comment. I defend anonymous commenting and you are most welcome here but I have to say that personal views/anecdotes which are neither signed nor backed up by evidence add little to the discussion. Your feedback that you have a hard time understanding what the issue is with the nanoflares is however very valuable and we will try to post a simpler more direct post at some point. For now, this letter to PNAS published as a preprint might be a good place to start?

      Liked by 1 person

  4. SmartFlares are also able to track miRNA and even exosomes. SmartFlares share same uses of Sticky-flares and some more.
    Take a look at:
    http://dev.biologists.org/content/142/18/3210.long

    They show endogenous production of miR-30d by hEECs and its secretion in exosomes that were identified by using a specific custom probe (SmartFlare, Millipore),
    Fig. 3. With EM images of exosomes labelled with the gold particle, also
    Figure 5 and Supplementary Figure 2 shows new interesting uses of SmartFlares as exosomal tracking tool and
    Supplementary Movie 1. Live animation showing the location of miR-30d in human luminal epithelium.

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    1. @ Caroline;

      Our involvement with SNAs started with an undergraduate project characterising the SmartFlare RNA detection probes. At least in our hands we came to the conclusion that they do not report on RNA levels but instead show fluorescent signal as a result of nuclease activity. This is why we (and many others) see a punctate fluorescent signal in SmartFlare-loaded cells.

      Please see http://bit.ly/1MmiTrR and enclosed links for more details on the project (which is an open science project so you can see all of the data for yourself).

      As regards the paper you reference, I feel that the authors largely misinterpret and overstate the SmartFlare data. For example, they show gold particles in vesicles and assume that the particles are detecting miRNA in the vesicles (instead of the simpler interpretation that the particles are taken up into cells in the vesicles whereupon they remain). Likewise, Figure 5 assumes that the miRNA is labelled with a fluorescent probe, which is the way the StickyFlares are reported to work, but not the SmartFlares.

      Also, I disagree with your point that Figure 3 shows exosomes labelled with gold. Vesicles maybe, MVBs perhaps, but without purifying exosomes and doing TEM, that’s simply overstatement. Even after purification still you have questions of contaminants.

      As I read the paper anyway, I put (most of) my comments on a PubPeer page at https://pubpeer.com/publications/26395145. Hopefully we can start a discussion about the paper there. I would invite you to add your comments and interpretation of the data, preferably following my lead and signing your name.

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  5. Thanks Dave, This paper is a journal club next Friday. I was trying to understand -a bit confused about smart flares and sticky flares. Looks like it will be very interesting.. I will fill the Conference Room. I am a PhD st, and I can not contribute, but for sure that after the JC I will.
    Thanks again

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