Packaging Precious Goods with Lethbridge Undergrads

I buy a lot of things online these days. It’s just so convenient to find something on Amazon and trust that it’ll get delivered to my doorstep at some point.

But if you think about it, there’s a lot of stuff that happens behind the scenes to get packages to their destinations. This is a problem that comes up in biotech quite often. The human body, for example, is quite good at protecting itself from foreign stuff. Stuff like bacteria, viruses, DNA, and proteins. Stuff like a new drug you’re trying to use to treat disease.

So how do you protect your precious cargo until it reaches where you want it to go? This is the problem that the University of Lethbridge iGEM team tackled this year. They’re building protein capsules that can hold small molecules so they can safely reach their destination.

Meet VINCEnT

They call their system the Viral-Inspired Novel Cargo Encapsulation Toolkit, or VINCEnT. (Again, I love a good acronym.) They even have him represented with an adorable mascot.

VINCEnT
No, seriously. Look at him.

VINCEnT is a system for building custom protein nanocompartments (PNCs). PNCs are basically little hollow shells that you can use to hold, protect, and transport specialized molecules. (Think hamsters in balls, except nano-sized and the hamsters are actually useful for something.)

The team made a helpful little video explaining what VINCEnT can do:

Source: Lethbridge iGEM 2018

Special Delivery

PNCs mimic a single feature of viruses while discarding everything else that would make it, well, viral.

Viruses normally infiltrate cells by pretending to be something good, so the cell lets them in. Once inside the cell, viruses can replicate by using their own DNA or RNA to make more of themselves.

With PNCs, there’s no DNA to replicate, so no new PNCs get made once they reach the cell. There’s also no other molecule involved except the one you want to deliver. So if you really dumb it down (and do the project no justice), PNCs are just boxes to hold cargo.

Viruses are very specific to particular cells. For example, cold viruses attack the upper airways but don’t affect skin cells. Most viruses don’t even affect humans. Instead, they attack other plants, bacteria, or even other viruses (…kind of).

PNCs take advantage of this feature. By “addressing” them to only particular cell types, you can deliver molecules precisely. That means that you can reduce off-target effects, which is good news for doctors and patients alike.

The Magical Self-Assembling Box

Imagine if your new IKEA dresser could just assemble itself when you put the boards, dowels, and cams close enough together. Don’t know about you, but it would have definitely saved me about two hours of exasperation back when I got mine.

Smug bastard
Apparently, they also kill.

The great thing about PNCs is that they self-assemble. They automatically come together to form little capsules without any extra effort. The Lethbridge team was able to show that purified PNC proteins can assemble into complete nanoparticles, as expected.

But can the PNC hold cargo while it’s assembling? In a collaboration with the University of Calgary’s iGEM team, the Lethbridge team showed that they could encapsulate the Calgary team’s CRISPR-Cas9 system in a type of PNC called P22. So yes, results look promising.

Unfortunately, due to time constraints, we haven’t seen if the Cas9 system works in these PNCs, but both teams are pretty optimistic. If you see them in Boston, you should ask about it.

There are a few other experiments they worked on for other applications, so you can check them out on their wiki.

Shipping Up to Boston

The team hopes that the VINCEnT system will help other researchers. Since the system is quite flexible, there are many ways that PNCs can be used in other projects in the future.

Be sure to keep in touch with the team on their Facebook and Twitter.

The team will be presenting their project at 2:45pm EST on October 26th. Good luck!

This is Part 3 of a six-part series showcasing the Alberta iGEM teams this year. Be sure to check out UCalgary’s and UAlberta’s projects if you missed them!

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