We are publishing today “The Spherical Nucleic Acids mRNA Detection Paradox“, the outcome of an open science project which started with an Hns student last year. In the last 12 months, we have reported in quasi real-time our experiments, protocols and analyses in an open science notebook and shared the data on our repository. The data are also stored at FigShare (e.g. Electron Microscopy results).
In addition to being exciting scientifically (he says!), this has been an experiment in how do science in the open using the tools of the 21st century to share information and solicit feedback. It is therefore fitting to publish it on a platform that challenges conventional modes of peer review.
We have chosen ScienceOpen where publication happens immediately (a couple of hours from submission to publication), followed by open peer review. In the coming weeks and months, I hope that many scientists will provide their expert evaluation of our article. In particular, Chad Mirkin will be invited to provide a review.
This article is important to all scientists who are using nanoparticles for imaging and sensing inside living cells. It should also be particularly relevant to past, current and prospective customers of the SmartFlares. Here is the abstract:
From the 1950s onwards, our understanding of the formation and intracellular trafficking of membrane vesicles was informed by experiments in which cells were exposed to gold nanoparticles and their uptake and localisation, studied by electron microscopy. In the last decade, building on progress in the synthesis of gold nanoparticles and their controlled functionalisation with a large variety of biomolecules (DNA, peptides, polysaccharides), new applications have been proposed, including the imaging and sensing of intracellular events. Yet, as already demonstrated in the 1950s, uptake of nanoparticles results in confinement within an intracellular vesicle which in principle should preclude sensing of cytosolic events. To study this apparent paradox, we focus on a commercially available nanoparticle probe that detects mRNA through the release of a fluorescently-labelled oligonucleotide (unquenching the fluorescence) in the presence of the target mRNA. Using electron, fluorescence and photothermal microscopy, we show that the probes remain in endocytic compartments and that they do not report on mRNA level. We suggest that the validation of any nanoparticle-based probes for intracellular sensing should include a quantitative and thorough demonstration that the probes can reach the cytosolic compartment.
The paper will be typeset in the next few days and open peer review will be open from that point. Comments are already possible. Thank you to Dave Mason, Gemma Carolan, Joan Comenge and Marie Held for their contributions to this work.