Update: we have submitted a Letter to PNAS as a response to the paper discussed below. It is currently available as a preprint.

The Mirkin group recently published the latest paper to use Spherical Nucleic Acid (SNA) technology that we’ve come to know and love as Smart/Nano Flares. In an interesting twist, instead of having target oligos bind to the nanoparticle (displacing fluorescent reporter sequences), the reporter sequences are now complimentary to the target oligos, labelling them directly. In theory this allows for dynamic labelled, tracking and quantitation of mRNA in cells.

I went over the paper in some detail. The technology is basically identical to SmartFlares (with capture and reporter oligos reversed) and will presumably therefore have the same problems with endosomal escape. Indeed the data in the paper do nothing to convince me of a cytosolic localisation, especially when you look at the two Supplementary Movies here and here which look remarkably similar to some of our stills of 10kDa dextran loaded into the endocytic pathway:

HeLa cells loaded with 10kDa fluorescently labelled dextran for 18h.

Having gone to the trouble of going over the paper, I added some points to a comment on PubPeer. You can join in the discussion here.


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