CAMBRIDGE, Mass. — AIRNA has presented new preclinical data for its lead RNA-editing therapeutic candidate, AIR-001, and for cardiometabolic research programs aimed at using RNA editing to address rare and common diseases.
The Cambridge biotechnology company said AIR-001 showed what it described as best-in-class potential in preclinical studies for alpha-1 antitrypsin deficiency, or AATD, a genetic disease that can cause progressive lung disease and liver injury. The data were presented at the 2026 annual meeting of the American Society of Gene and Cell Therapy in Boston.
AIRNA said AIR-001 achieved up to 59% precise RNA editing in vivo and restored more than 40 µM of functional M-AAT in a mouse model of AATD. The company said the results support the potential of its RNA-editing platform to both repair disease-causing variants and introduce protective variants associated with improved health.
“We are excited to showcase for the first time our robust preclinical data for AIR-001 — now being evaluated in the clinic — as well as new data that illustrate the breadth of AIRNA’s RNA-editing platform,” said Sriram Sathy, Ph.D., chief scientific officer of AIRNA. “From repairing disease-causing variants to introducing protective variants, we believe RNA editing offers a powerful and flexible approach to therapeutic development.”
AIR-001 is designed to correct the most common disease-causing mutation of AATD, known as PiZ, at the RNA level. The therapy is delivered by subcutaneous injection as a GalNAc oligonucleotide.
In a mouse model of AATD, AIRNA said AIR-001 produced potent and precise editing of the PiZ mutation, with no off-target edits observed. The company said editing in liver RNA increased with higher doses, with a 10 mg/kg dose achieving 59% editing, more than 40 µM of corrected alpha-1 antitrypsin in serum and 70 µM total AAT.
A longer-term mouse study found that biweekly AIR-001 dosing for 15 weeks increased levels of M-AAT and total AAT over time, suggesting potential for longer-term benefit. The company also reported improvements in lung- and liver-related disease endpoints, including a more than 30-fold increase in neutrophil elastase inhibition.
In non-human primate studies, AIRNA said AIR-001 showed tolerable and durable liver exposure, supporting the possibility of dosing once every eight to 12 weeks in humans.
AIRNA also presented preclinical proof-of-concept data from its cardiometabolic RNA-editing programs, including work targeting low-density lipoprotein receptor, or LDLR. The company said it developed an RNA-editing oligonucleotide designed to replicate the effect of a protective LDLR gene variant associated with substantially lower LDL cholesterol.
In human hepatocytes, the editor achieved up to 70% editing and a 3.5-fold increase in LDLR expression, AIRNA said. In a humanized mouse model, treatment led to a 92% reduction in LDL cholesterol. The company said combination dosing with alirocumab, an approved anti-PCSK9 antibody, produced greater LDL cholesterol reduction at lower doses than alirocumab alone.
AIRNA also reported data from research targeting apolipoprotein B, or ApoB, a cardiovascular disease target where previous therapeutic approaches have been limited by liver toxicity. The company said it identified a protective APOB variant associated with lower LDL cholesterol without liver-related health issues and used RNA editing to reproduce the effect of the variant.
In vivo, the ApoB program achieved 30% editing, a 21% decrease in ApoB protein and a 17% reduction in LDL cholesterol, with no observed hepatotoxicity, AIRNA said.
AIR-001 has received orphan drug designation from the U.S. Food and Drug Administration for the treatment of alpha-1 antitrypsin deficiency and is being evaluated in the Phase 1 RepAIR1 clinical trial.
