The creation of the (adorable) Woolly Mouse-mmoth!

Colossal Biosciences bills itself as a de-extinction company with the goal of resurrecting long-lost animal species like the woolly mammoth.

Although, that seems to maybe not be an accurate picture of what they're actually doing, which is mutating genes in extant (not extinct) animals to make them LOOK LIKE an extinct animal.

Those are two very different things.

But resurrecting extinct animals, especially ones that weren't well preserved, or that are thousands of years old, is impossible.

This is because the half-life of DNA is about 500 years, so anything older than 500 years is going to have a genome that's a jumbled mess unless it was preserved under pristine conditions.

But even our Woolly Mammoth friends who have been trapped in the Siberian Tundra for eons weren't preserved well enough for us to extract some nuclei and Dolly up a copy 🐑.

So, the next best thing is to make an animal that looks like the thing that went extinct.

How does one go about making a Woolly Mammoth look-a-like?

Well, you start with an elephant, and then give it long, flowy locks!

At least, that's the plan, but elephants are tough customers when it comes to making genetically modified versions because they have a 22-month gestation period.

Waiting 2 years to see if what you did worked isn't exactly a rapid turn around.

So, Colossal have instead done a bunch of their early editing work in mice!

What they've come up with can be seen in the figure above where they multiplex edited a mouse to give it a Woolly appearance.

They selected a number of genes already known to produce abnormal hair morphology in mice and combined them together with a couple of other genes observed to be mutated in mammoth genomes.

A) is an overview of how they did the CRISPR editing, B) shows a graph of how they screened for the best guide RNAs (CRISPR/Cas uses these to make their targeted cuts) - the orange ones are the ones they used for multiplex editing, C,D,E,F) the researchers performed two editing experiments and the efficiency of the editing in each embryo line can be seen in the tables and charts, G) shows there were few off target effects and none that damaged other genes, and H) is the pièce de résistance which displays the cute little fur balls that were created!

Colossal went on to show that they can also use cytosine base editing to get similar results.

This paper is important because genome engineering has come a long way since the early days of CRISPR, and this work highlights that it can now be highly efficient, rapidly producing animals with a desired phenotype.

And, while all the chatter about "de-extinction" is fun, that's not what Colossal is doing here.

What they've actually done is develop a multiplex editing platform to create chimeric animals and cells for use in agriculture or the pharmaceutical industry.

This is still interesting, but we shouldn't pull the wool over people's eyes about bringing extinct animals back into existence.