AIRNA's RNA Editor Sidesteps DNA in AATD Correction

Most therapeutic editing strategies rely on engineered nucleases or base editors that permanently change the genome. AIRNA's RESTORE+ platform instead hijacks adenosine deaminase acting on RNA (ADAR), an endogenous human enzyme that edits adenosines to inosines in cellular transcripts. A short oligonucleotide base-pairs across the target adenosine in the mRNA, recruiting ADAR to deaminate the A to I, which the ribosome reads as guanosine. The genome is untouched.

The approach brings clear advantages over CRISPR-Cas. Because ADAR is already present in human cells, there is no need to deliver a bacterial nuclease that can provoke immune responses. And the absence of permanent genomic changes means treatment can be stopped or titrated if problems emerge. The principal limitation is that ADAR can only convert adenosine to inosine, and only at adenosines in a suitable sequence context, so the technology is restricted to mutations that fit this narrow chemistry. Moreover, patients need to be redosed for life rather than treated once.

AATD fits that scope unusually well. The PiZ allele responsible for most clinical disease is a G-to-A substitution in SERPINA1, so the corrective edit is exactly the A-to-G change ADAR performs. The therapeutic goal is to raise circulating wild-type protein – something RNA editing achieves directly but knockdown approaches cannot. The liver, where misfolded Z-AAT polymerises, is also readily reached by the GalNAc-conjugated chemistry AIR-001 employs.

»From repairing disease-causing variants to introducing protective variants, we believe RNA editing offers a powerful and flexible approach to therapeutic development,« Sriram Sathy, chief scientific officer of AIRNA, says in a press release.

In NSG-PiZ mice, a single subcutaneous dose produced 59% editing of SERPINA1 in the liver, corresponding to 70 µM total AAT and over 40 µM corrected M-AAT in serum on day 7. Bi-weekly dosing over 15 weeks generated accumulating M-AAT and a greater than 30-fold rise in neutrophil elastase inhibition, with significant reductions in hepatic AAT aggregates and immune cell infiltration. No bystander or off-target edits were detected.

Non-human primate work showed a two-fold longer oligonucleotide half-life than in rodents, supporting a projected dosing interval of every 8 to 12 weeks – well below weekly plasma-derived augmentation, though still short of the single-administration ambition of DNA-level editing.

If the 40 µM preclinical exposure can be approached in patients, AIR-001 would clear the 11 µM threshold cited as protective against emphysema by a comfortable margin – and validate ADAR editing as a clinical modality.

The data was presented on 12 May 2026 in a press release and in abstract #77 at the American Society of Gene and Cell Therapy (ASGCT) meeting, a study led by Anindya Sen and Sriram Sathy at AIRNA Corporation.