Grabbing viruses at the nanoscale

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Today we have a great paper, using DNA nanorobots to grab particles at the nanoscale!

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Grabbing viruses at the nanoscale

Nanorobots, in my humble opinion, are the absolute coolest thing in the nanotechnology toolbox. The possibilities opened up by the ability to perform tasks at the nanoscale are endless: better precision medicine, more efficient catalysts, new and greener materials. And nature has its own tiny machines, made of proteins, RNA or DNA that self-assemble inside cells. So, what could be better than borrowing a page from nature’s playbook to create artificial nanorobots? (Spoiler: not much.)

This idea lies at the heart of today’s paper (well, more or less). The team behind it decided to apply classic mechanical design at the nanoscale, to create one of the basic function of macroscale robots: grasping (or gripping?). And of course, what better technique to create robots with nanometer precision than our trusted DNA origami? DNA origami (the technique where nanostructures are created by folding a long single stranded stretch of DNA together with a bunch of shorter single stranded DNAs ) offers great biocompatibility, precision and programmability, ideal to create nanorobots. The authors set themselves an ambitious goal: to mimic the dexterity of the human hand (or the bird claw, or bacteriophages, whatever you prefer) at the nanoscale. Very cool!

Unfortunately, previous nanorobots don’t really show the dexterity and versatility needed for the job. So, the authors designed their own DNA NanoGripper (nice name choice there). This NanoGripper features a central palm and four flexible fingers, each with three movable phalanges. Cleverly, they designed it as a single DNA origami structure, making synthesis simpler (assembling multiple DNA origami pieces can be a headache). They also optimized the NanoGripper’s dimensions to wrap around objects in the 50–100 nm size range, just right for viruses or nanoparticles. To top it off, they modified the fingers to attach DNA aptamers for specific target recognition.

So, once the researchers had this very cool structures, what did they do with them? Well, glad you asked. The team’s first goal was to demonstrate its potential for biomedical applications. They functionalized the NanoGripper’s fingers with aptamers targeting the spike protein of SARS-CoV-2 (a popular target lately). Once bound to the virus, the NanoGripper generated a fluorescent signal. They also used a fluorescence amplification strategy called photonic-crystal enhanced fluorescence, which provided a crazy 250-fold signal amplification! With this setup, they detected as few as 100 virus copies per milliliter of saliva in just 30 minutes. That’s on par with, or even better than, RT-qPCR, the gold standard for virus detection, all without the hassle of RNA extraction, purification, and amplification.

But they didn’t stop at viruses. To highlight the NanoGripper’s versatility, they functionalized its fingers with other ligands, like single-stranded DNA and biotin. This allowed it to capture gold nanospheres and spiky gold NanoUrchins. Even more impressive, the NanoGripper significantly enhanced the detection of these particles!

The grand finale? Testing whether the NanoGripper could block SARS-CoV-2 from entering host cells. The idea is that by attaching multiple aptamers, the NanoGripper can create a strong interaction with viral spike proteins, and this physical barrier can block the virus from interacting with the cells. And the NanoGripper proved quite good at this: flow cytometry and confocal microscopy showed up to 99% reduction in viral entry into the cells!

What I found particularly exciting was the NanoGripper’s versatility. Beyond the sheer coolness of grasping nanoscale objects, the team showed how this structure could be adapted for various uses, like enhancing detection sensitivity in biosensing or environmental monitoring, where dilute targets (like pathogens in water) are often the norm.

All in all, this was a cool paper, and you can read all of it here!

More room:

• Exploring triplex DNA in cells: Triplex DNA is a form that most people forget about, but is a crucial regulatory element. This study used a highly specific chemical probe and proximity capture and the researchers identified a diverse set of proteins interacting with triplex DNA in living cells. These findings offer a comprehensive resource for understanding triplex DNA biology and its therapeutic potential.

• Fast synthesis of DNA origami crystals: If you feel inspired to make nanocrystals from DNA origami, this paper will make your life easier. The authors introduce a method using urea to rapidly synthesize high-quality DNA origami crystals at room temperature. Crystals form within 4 hours and grow to ~5 micrometers in 2 days, without precise instruments. A phase diagram enables customizable melting temperatures, ensuring high-quality crystals even in fluctuating conditions, and this could pave the way for industrial scale DNA nanostructures!

• Directing materials for nanofabrication: If you want to know more about the latest advances in assembly-based 3D nanofabrication, this is your review. Recent methods are categorized by mechanisms like chemical reactions, physical interactions, and synergistic forces. With progress in resolution, material compatibility, and cost efficiency, 3D nanofabrication is poised to transform fields like robotics, sensors, and photonics. Let’s hope they are right, for my job prospects.

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