Editing human DNA has entered the public consciousness in a big way in recent years with its increasing use in laboratories—and, in recent news that shocked the scientific community, in embryos—of tools such as CRISPR-Cas9.
Locana, a gene therapy biotech in San Diego, is taking what it describes as a “parallel path” to developing therapeutics that could potentially fix diseases by changing our genetic code through altering DNA’s molecular compatriot, RNA. Tweaking RNA may let scientists avoid some of the concerns swirling around editing DNA—our genetic map—such as the risk that subsequent generations could inherit any gene edits. RNA molecules are messengers that shuttle genetic instructions about how to make proteins to a cell’s protein-making machinery.
Locana was founded in 2016 based on technology developed by Gene Yeo and David Nelles in their lab at UC San Diego and licensed from the university. Nelles is Locana’s chief technology officer; Yeo, who has been involved in founding a number of startups, is chairman of the scientific advisory board. (Yeo also was one of two Big Idea winners at the first-ever Xconomy Awards San Diego, held last month.)
The team published a paper that year in Cell that showed how the lab had tweaked CRISPR-Cas9 to track RNA molecules, which allows scientists to monitor the strands as they move around in live cells.
At first, Yeo said he thought the best use of the discovery would be as a diagnostic tool.
But in 2017, Ron Batra, Locana’s vice president of research and development, published another paper in Cell showing that, in the lab, the company had figured out how to get CRISPR to target the RNAs with certain repeated sequences in three genetic diseases known to be caused by these repeats: muscular dystrophy, Huntington’s disease, and amyotrophic lateral sclerosis (ALS).
That changed the company’s aim from diagnostics to therapeutics, and Locana raised seed capital from three institutional investors: Arch Venture Partners, Lightstone Ventures, and Temasek, a Singaporean sovereign wealth fund.
Arch, Temasek, and Lightstone were joined in Locana’s $55 million Series A round of funding last month by new investors, including GV (previously Google Ventures) and a strategic investor, Belgian pharma company UCB’s venture arm, UCB Ventures.
Jeff Ostrove, a Locana board member who was appointed CEO this year, says the cash infusion will allow the company to expand its headcount from five to approximately 30. The startup is also relocating from the JLabs incubator to its own office in San Diego.
Ostrove previously headed two gene therapy developers: AbVitro, which was acquired by Juno Therapeutics (now part of Celgene in 2016, and Ceregene, which was acquired by Sangamo BioSciences (NASDAQ: SGMO) in 2013.
Ostrove said Locana has data in multiple diseases, but isn’t yet disclosing its lead indication.
“We have the ability, scientifically, to go after dozens of different diseases that share some defect within the RNA,” he said.
He wouldn’t share when the company might start testing in humans. The money Locana has raised is enough to move at least one program into the clinic and to ready others for human trials, although not necessarily to run those studies, he says.
In addition to the backing from venture investors, the company last week received a vote of confidence from the Muscular Dystrophy Association: a $550,000 grant through the MDA’s Venture Philanthropy program to advance its research for a potential treatment for myotonic dystrophy (DM), a genetic disease that causes progressive muscle weakness. About 1 in every 8,000 people worldwide—roughly 40,000 in the US—are estimated to have the disease, which is the most common form of adult-onset muscular dystrophy, according to the National Institutes of Health. The MDA has committed more than $1 billion to research into neuromuscular diseases and is the largest nongovernmental source of funding for research into the disorders, which include MD and ALS.
Lynn O’Connor Vos, MDA’s president and CEO, said the recent FDA approval of the first gene therapy for a neuromuscular disease—the Novartis (NYSE: NVS) spinal muscular atrophy treatment Zolgensma—gives the association hope that approaches such as Locana’s could one day treat people living with muscular disorders.
“The relationship is an important one, not just because of the financing, but because of the confidence that they have in the company and what we can achieve,” Yeo says.
Locana isn’t the only company researching alternative approaches to gene editing. Boston-based Beam Therapeutics says it can edit DNA and RNA precisely, targeting just a single base pair out of billions. The company uses CRISPR to target a single base without cutting the DNA or RNA strand for a more precise method of editing.
Beam, which raised $135 million earlier this year, shares some investors with Locana, including Arch and GV.