❉ Does Evan Know What He’s Talking About? ❉
I know enough about biochem to ingest the paper and that’s about it.
Before I tear off on these things as an ingenious drug delivery vector, gotta highlight one of my favorite scientific graphics lifted from Douglas et al.
The paper describes a two piece hexagonal barrel assembled from DNA strands and held together by short DNA "staples." You can stick a payload in the center and design the staples to lose their grip on the barrel halves if the right molecule hits them, e.g. a certain protein on the surface of a cell. I sketched out the shape to the left.
Now that you know what they're talking about, here's the graphic: lovely first, and a great explainer if one spends a bit of time with it.
A explains the basic idea: load up the barrel (seen head-on) with a payload, and if the surface protein on a cell unlocks it, that'll be indicated by the flow cytometry counts (the hump on the graph will be on the right).
B demonstrates how if you key the "staples" to two different triggers, you can make a biological AND gate: 0 and 1 gets 0, 1 and 0 gets 0, 1 and 1 gets you 1. Gotta satisfy both conditions to get that barrel to unlock and release the payload, making this thing very specific in terms of what it throws that payload onto. See how this could make a good drug delivery system?
C shows the results of the "dump these things in with cancer cells, see if it delivers the payload only to the correct targets" test. Each box represents a different type of cell population these devices were thrown into, each with a different set of surface receptors (represented as colored keys). The row labels show what kind of staple set each structure was equipped with; if it had one of each type, that makes the hyper-specific AND gate we were talking about.
And those colored waves? Remember, a hump on the left means low payload release, and a hump on the right means a bunch of payload dumped out. The dual black closed locks meant that nothing unhooked those staples, so no payload released, so the humps in that row are all on the left. The dual grey open locks means those things opened willy-nilly and always dumped payload, so a bunch of humps appear on the right.
For the rest of the types, mixes of blue, yellow and red locks, you can immediately read down each cell and see that the staples did their job of holding closed when they needed to and popping open when presented with the right "keys": the second box from the left had all keys floating around in there, so every type of device popped open. On the far right, only the blue key was present, so only the device that needed just blue keys opened up. Every other type needed more than one color (remember, AND gate, only 1 and 1 gets you 1) stayed shut. These things are specific as hell, believe it.
Science later, cute now, this is all the beauty you will ever need.