Jacob Kimmel

Beyond just which genes do I want to move up and down and which gene perturbations do I put in, you then need to know, what cell state am I engineering for?

What do I want

I love that one.

Potentially.

Potentially.

So the original procedure is created by a bunch of brilliant folks.

There's a group in Ido Ahmed's lab at the Weizmann Institute, Aviv Regev's lab at the Broad, where Trey Dixit, a friend of mine, helped work on this, and then Jonathan Weizmann's lab at UCSF, where Britt Adamson did a lot of the early work.

They all constructed this idea where you can go in and you label a perturbation that you're delivering to a cell.

So this is typically a transgenic perturbation, meaning you're integrating some new gene into the genome of a cell, and that turns another gene on or off.

They used CRISPR, but there's lots of ways to do it, and the concept's pretty general.

And then you attach on that new transgene, that new gene you put into the genome of the cell, some barcode that you can read out by DNA sequencing.

So now when you rip the cells open, you're able to not only measure every gene they're using, but you also sequence these barcodes and you know which genes you turned on and which are off.

So you can then start to ask questions like, well, I've turned on genes A, B, and C. What did it do to the rest of the cell?

So that's the general premise of the technology.

And so it's useful to just set that up because it explains why this didn't all happen earlier.

One, the actual readout, ripping the cells open and sequencing them, used to be pretty bad and it used to be really expensive.

And it's gotten much better over time.

So the metric people often think about here is like cost per cell to sequence.

It used to be measured in dollars and now it's measured in cents and down to the fractions of cents because that cost curve has made it...

has improved dramatically.