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Start-ups

Twentyeight-Seven Therapeutics launches to boost anticancer microRNA with small-molecule drugs

With $65 million raised, 28-7 is developing inhibitors of the Lin28 protein to boost levels of an anticancer microRNA called let-7

by Ryan Cross
September 12, 2018 | APPEARED IN VOLUME 96, ISSUE 37

 

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Credit: Ryan Cross/Piotr Sliz/NGL Viewer PDB ID 5UDZ
A crystal structure of the protein Lin28 binding the microRNA let-7 (magenta).

Twentyeight-Seven (28-7) Therapeutics is the latest start-up to launch with the goal of developing drugs that tackle the tricky interface between RNA and proteins. And it’s got a whopping $65 million in series A financing to do it.

The company’s name comes from a protein called Lin28, which binds and blocks the microRNA let-7. In healthy adults, let-7 suppresses genes that can cause cancer if left unchecked. In the past decade, researchers have discovered a loss of let-7 or an uptick in Lin28 in a long list of human cancers.

One of those researchers is Harvard Medical School scientist and current dean George Daley. In 2016, Daley and three other Harvard scientists—Richard Gregory, Frank Slack, and Piotr Sliz—founded 28-7 to develop small molecules that inhibit Lin28 in cancer cells, thereby boosting levels of let-7. Earlier this month, the company emerged from stealth mode to showcase its ambitions.

CEO Kazumo Shiosaki explains that at first, the team was worried that the interaction between Lin28 and let-7 would be too hard to modulate with drugs. Proteins and RNA often interact with no clear foothold for a drug to latch on to. But when Sliz solved the crystal structure of the human Lin28/let7 interaction, he spotted structures in the interface that looked druggable. “Those data made us feel like we had a chance,” Shiosaki says.

28-7 is already thinking about new targets too. One is a kind of enzyme called a terminal uridylyltransferase, or TUTase. Once Lin28 binds let-7, it recruits a TUTase to place a molecular tag on let-7, which marks it for degradation by an RNA-chopping enzyme. Preclinical studies by the firm’s founders have shown that this TUTase is another promising target for inhibition, Shiosaki says.

For now, 28-7 isn’t disclosing how far the $65 million will get it, or when it expects to test its first compounds in humans. The investment “is a real statement of the promise and opportunity” of drugging RNA-modulating proteins, Shiosaki says. “There is just a lot of excitement about RNA biology.”

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