A Study of AIR-001 in Adults With Alpha-1 Antitrypsin Deficiency (AATD)

This is a Phase 1, open-label, single ascending dose (SAD) and multiple dose (MD) study of AIR-001 in participants with alpha-1 antitrypsin deficiency (AATD) due to PiZZ genotype.

Inclusion Criteria: 1. Male or female participants \>18 years and \ 10 kPa defined by screening liver elastography, historical liver biopsy showing ≥ F3 fibrosis (METAVIR or comparable scoring system), or established diagnosis of hepatic cirrhosis. 8. Any of the following screening laboratory abnormalities: 1. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT) \> 3 x upper limit of normal (ULN) 2. Total bilirubin \> ULN (note: for participants with documented Gilbert's syndrome and direct bilirubin ≤ ULN , exclusion criterion is total bilirubin is \> 2.5 mg/dL) 3. INR \> ULN (for participants taking stable doses of anticoagulants, the exclusion criterion is INR \> 3.0) 4. Platelet count ≤ 150 k/μL 5. Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m² by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation 6. Urine Albumin-to-Creatinine Ratio \> 300 mg/g 7. Urine Protein-to-Creatinine Ratio \> 500 mg/g 9. Prolonged QT interval on electrocardiogram (ECG), defined as QTcF ≥ 450ms (men) or ≥ 470ms (women) 10. ECG findings at screening that render measurements of QT interval imprecise. 11. History of congestive heart failure, serious cardiac arrythmias requiring anti-arrhythmic medications or unexplained black-outs or fainting episodes with a suspected cardiac origin 12. Positive screening test or known chronic infection with Hepatitis B, Hepatitis C, or HIV. 13. Known history of coagulopathy or bleeding diathesis 14. History or intolerance to subcutaneous (SC) injection including relevant dermatological conditions affecting standard injection sites 15. History or presence of any medical condition, behavioral or psychiatric disorder, or planned surgical procedure or surgical history that may interfere with participation in the study or interpretation of study results, and/or put the participant at significant risk (in the opinion of the investigator) if he/she participates in the study. 16. History of any lung-volume reduction procedure in the 6 months prior to screening. 17. Laboratory value(s) outside the laboratory reference range that is (are) considered to be clinically significant and may affect the safety, efficacy, PK, or PD assessments or interpretation by the Investigator, at screening 18. History of alcohol or drug abuse within the past three months 19. Current or previous participation in any other clinical study where the participant has received a dose of an IMP within 3 months or 5 half-lives of the IMP, whichever is longest, prior to Screening Visit 20. Any previous gene replacement or DNA-editing therapy 21. Any previous use of an RNA-based therapeutic (except for AIR-001 or RNA-based vaccines) within the 6 months prior to the Screening Visit or at any time if stopped due to drug-related adverse event. 22. Use of any new prescription, vaccine, herbal remedy, over-the-counter medication, or supplement, or changes in chronic therapies within the 28 days prior to dosing unless approved by study Medical Monitor.