Atlas unveils RNA-editing Korro Bio helmed by Nessan Bermingham

DNA
“We are not looking to shut down genes, but to modify RNAs and move them from a diseased state to a normal state through base targeting," said Korro CEO Nessan Bermingham. (LionFive/Pixabay)

Nearly two years ago, Nessan Bermingham, Ph.D., handed the reins of Intellia Therapeutics over to John Leonard, M.D., the R&D chief who had built the company alongside him. After a break, he landed at Atlas Venture, the VC firm that helped launch Intellia in 2014 and that is now debuting Korro Bio, Bermingham’s latest project. 

Korro is based upon the work of Josh Rosenthal, Ph.D., of the Marine Biological Laboratory in Massachusetts, an affiliate of the University of Chicago. The Cambridge, Massachusetts-based biotech is launching with funding from Atlas and New Enterprise Associates but is keeping the amount under wraps for now. 

Rosenthal’s, and now Korro’s, approach relies on nucleotide deamination, an endogenous RNA-modifying process that already happens in cells. Specifically, it takes advantage of a family of RNA-editing enzymes called adenosine deaminase acting on RNA (ADAR). This group of enzymes deaminates the nucleotide adenosine (A) to make inosine (I), which is read as guanosine (G) inside cells. 

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RELATED: After a round trip, ex-Intellia CEO Bermingham lands back at Atlas 

Korro’s ADAR approach doesn’t permanently edit the genome by making a double-stranded cut in the DNA, like CRISPR systems do. 

“We are not looking to shut down genes, but to modify RNAs and move them from a diseased state to a normal state through base targeting versus shutting the gene off,” Bermingham told FierceBiotech. 

“There is a large number of indications that this approach can be applied to, where there are G-to-A mutations. The intention is to convert them back,” he said. 

It's still early for Korro to be disclosing indications, but Duchenne muscular dystrophy and Parkinson’s disease are two areas in which G-to-A mutations play a role. And Bermingham mentioned that the “easily deliverable, closed compartment” areas such as the central nervous system, muscle, liver and eye would be natural areas of focus for a technology like Korro’s. 

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And that’s not all—exploiting a process that cells already do gives Korro’s ADAR technology an advantage over other gene-editing or gene therapy approaches. 

“If we think about how we deal with things from a gene therapy standpoint, I’m going to shove as much of this stuff as I possibly can into you so I can make as much of this protein as I can to rectify this disease,” Bermingham said. 

But it’s not as simple as that: “It’s not like for every gene, it’s on and stays on at a very high level until you die,” he said. “There is a cyclical nature to the expression of genes … As you think about being able to go in and fix mutations or variants, you want to ensure that the regulatory elements that control the expression of the gene remain intact. Going after RNA that has already been expressed means the regulatory system is normal.” 

Targeting an endogenous process also means packaging fewer treatment components and therefore more flexibility when it comes to delivery methods. 

With CRISPR-Cas9 systems, the delivery vehicle has to carry the actual gene-cutting mechanism, Bermingham said. With Korro’s approach, that RNA-editing protein is already in the cell. 

“All we need to do is recruit it to the target site. It simplifies delivery and manufacturability,” he said. 

That said, there’s a lot of work ahead for Korro. After incubating at Atlas, the company is now exploring the RNA transcripts of multiple genes that play a role in various diseases and working to build its team.

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