Designed switch allows unprecedented control over cells

#1

An incredible advancement. One of the first de novo proteins, and has a broad potential.

LOCKR can be “programmed” to modify gene expression, redirect cellular traffic, degrade specific proteins, and control protein binding interactions. The researchers also use LOCKR to build new biological circuits that behave like autonomous sensors. These circuits detect cues from the cell’s internal or external environment and respond by making changes to the cell. This is akin to the way a thermostat senses ambient temperature and directs a heating or cooling system to shut itself off as soon as a desired temperature is reached.

“In the same way that integrated circuits enabled the explosion of the computer chip industry, these versatile and dynamic biological switches could soon unlock precise control over the behavior of living cells and, ultimately, our health.”

Having no counterpart in the natural world, LOCKR stands apart from every tool of the biotech trade, including recent technologies like optogenetics and CRISPR. While its predecessors were discovered in nature and then retooled for use in labs, industry, or medicine, LOCKR is among the first biotechnology tools entirely conceived of and built by humans.

The July Nature papers reporting these findings are titled “De novo design of bioactive protein switches” and “Modular and tunable biological feedback control using a de novo protein switch.”

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#2

Fascinating. I like this part from a different article:

There are patents pending for LOCKR’s commercial use, but its creators have made the system freely available to academics. Any scientist with an Internet connection can access the blueprint for LOCKR: the DNA code used to build the string of the amino acids that builds the protein. “Not a single physical piece of DNA was exchanged between our labs,” El-Samad said. “The only thing that was exchanged between our labs through this collaboration was a file that had the DNA sequence.”

Biologists can print the code for LOCKR onto a custom strand of DNA and insert this into a cell. El-Samad envisioned an injection of cells, programmed with LOCKR circuits, as a method to control brain inflammation after a traumatic injury, for instance.

“You will start seeing uses for LOCKR in mammals and explorations for therapeutic uses — well, actually, it’s already begun,” Baker said.

This should accelerate further development of applications.

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#3

What does this mean for us in terms of advantages over existing crispr technology?

#4

I’ll have to look into it in detail when I have time (RIP my to do list…) but from what I have read it seems they are very confident in its ability to leverage cellular mechanisms. Nature is a highly prestigious journal of course, so this must be quite a solid methodology and result.

In terms of difference to crispr: Methylation is a buzzword here lately (even if not often understood) for the reason it was mentioned in a study of PFS patients, and obviously methylation is highly likely to be implicated in PFS, and how the site and severity-variable dysregulation of the AR is persistent. A year ago I posted a study regarding how crispr was used to effectively deliver tet1 payloads and cause precision demethylation: Editing DNA Methylation in the Mammalian Genome. This technique is being used in current research into disease.

Until we have much greater molecular level information as to the key loci(s), and likely new scientists working on the issue we are planning to reach out to, it’s moot what the advantages are or will be. Our sole focus is finding out what needs to be done, which won’t take care of itself as research into these technologies will. But it’s extremely positive that there’s another “easy” way to skin a cat when it comes to the control of gene expression.

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