As the next generation of nucleic acid editing technologies begin to pick up more steam — and more attention from venture capitalists (VCs) and pharma alike — AIRNA has raked in an additional $60 million, bringing its series A total to $90 million. The financing will help progress its lead RNA-editing therapeutic into the clinic for alpha-1 antitrypsin deficiency (AATD).The fresh funds come less than a year after AIRNA emerged from stealth with an initial $30 million from ARCH Venture Partners. The VC, along with existing investor ND Capital, joined in on Wednesday’s round, which was led by Forbion and saw participation from other new backers including Ono Venture Investment and Alexandria Venture Investments. The cash will also go towards expanding AIRNA’s pipeline, CEO Kris Elverum told FirstWord. “What we've also found, in addition to AATD, is that we have a lot of other therapeutic opportunities with our approach,” he said. “It's a different kind of opportunity when your science is going so well, it's almost incumbent upon us, it's our responsibility, to then move that forward and move it into patients.”ADAR risingAIRNA’s RESTORE+ platform is centred on using oligonucleotides to recruit endogenous ADAR enzymes to make precise RNA edits.The ADAR editing system works by having an enzyme bind to double-stranded RNA and convert adenosine (A) to inosine (I), which is interpreted by the cell’s translational machinery as guanosine (G). The ADAR family was first discovered in the 1980s, but it wasn’t considered a therapeutically or commercially feasible editing tool until 2019, Elverum said, when Thorsten Stafforst’s lab at the University of Tübingen showed that oligonucleotides could effectively engage with the enzymes, rather than having to rely on a fusion system using guide RNAs. Stafforst is one of AIRNA’s scientific co-founders, along with Jin Billy Li, a professor of genetics at Stanford University. Since then, the RNA editing technology has exploded in popularity due to the potential for ADAR to surpass its DNA-editing counterpart CRISPR by offering a more flexible way to address genetic diseases, without causing permanent changes and potential damage to the DNA. At least nine biotech startups have revealed ADAR-based editing platforms, and Eli Lilly, Roche and GSK have each made multi-billion-dollar bets on the technology. For more on the RNA-editing landscape, see Spotlight On: The growing universe of RNA editing technologies.Flexible editingIf DNA editing is analogous to making changes to our bodies’ hardware, then RNA editing is like a software update, Elverum said. “RNA editing is very unique because our drug product is temporary. We can dose up or down, we can start or stop, and it's very safely administered,” he added. ADAR also offers the opportunity to expand beyond the possibilities of DNA editing, which can be a bit of a one-editing-trick pony. Rather than just repairing genetic mutations, “RNA editing has the really unique potential to flip the concept of editing on its head,” Elverum explained, listing several possible uses such as introducing protective variants, making gain-of-function edits, or preventing protein-protein interactions. That flexibility could also help RNA-editing therapeutics be viable treatment options in a broader swath of diseases, including cardiovascular, metabolic and haematologic disorders. “If you think about the root-cause biology of a lot of large indications, it's at the RNA and protein level, and what that means is it allows us, with RNA editing, to go after targets that are unable to be accessed by other modalities,” Elverum said. “And that's where I get really excited about the long-term potential of what we can do.”AATD race To start, however, AIRNA is looking to establish proof-of-concept for its ADAR technology’s mutation repair capabilities, which is why the first indication the company is going after is AATD — a rare lung and liver disease caused by a G to A mutation in the SERPINA1 gene, which prevents the production of the alpha-1 antitrypsin protein. Elverum said AIRNA’s product will be subcutaneously administered on an infrequent basis and has best-in-class potential in regards to both potency and safety. At least one other biotech has already begun clinical testing of an ADAR-editing therapy in AATD. Wave Life Sciences started a Phase Ib/IIa study of its WVE-006 programme in June, and expects to have proof-of-mechanism data by year-end. For more on the candidate, see Spotlight On: RNA editing marches towards the clinic.