Study of YOLT-202 in the Treatment of Alpha-1 Antitrypsin Deficiency (AATD)

Inclusion Criteria: * Male or female (inclusive) aged ≥ 18 and ≤ 70 years old at the time of signing informed consent. * Diagnosed with AATD and genetically confirmed as homozygous PiZZ mutation. * Blood total AAT level \< 11 μM or equivalent protein in mg/dL. * Patients receiving augmentation therapy must be willing to discontinue it at least 6 weeks prior to signing the informed consent form (ICF) and throughout the study period, unless clinically indicated. Exclusion criteria * Body mass index (BMI) \> 35 kg/m2. * Patients who have undergone lung or liver transplantation, are on the waiting list for lung or liver transplantation, or have had lung volume reduction surgery (LVRS). * Clinical evidence of severe bronchiectasis, as judged by the investigator (e.g., excessive sputum production or recurrent infections requiring antibiotics \[\> 4 times per year\]). * FEV1 ≤ 30% of predicted value after bronchodilator use at screening * Liver disease with any of the following: * Measured liver stiffness (FibroScan) ≥ 10 kilopascals (kPa). * Known history of hepatic cirrhosis or associated complications (e.g., varices, ascites, hepatic encephalopathy). * ≥ F2 hepatic fibrosis in patients with prior liver biopsy. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 times the upper limit of normal (ULN). * Total bilirubin \> ULN; or \> 2 times the ULN if Gilbert's syndrome is documented. * International normalized ratio (INR) ≥ 1.2 at screening. If deemed appropriate by the investigator and/or the prescribing physician, anticoagulants may be discontinued for a washout period or reversed with vitamin K. If necessary, a repeat INR \< 1.2 is acceptable. * Hepatitis B surface antigen (HBsAg) positive. * Hepatitis C virus (HCV) antibody positive. If HCV antibody is positive, HCV RNA PCR must be negative. * Allergy to the drugs contained in lipid nanoparticles (LNP) or LNP-mRNA vaccines, or previous history of adverse reactions to LNP-based drugs; * Smoking more than 5 cigarettes per day or consuming the equivalent amount of nicotine or nicotine replacement products within the past 6 months before screening. * History of alcohol abuse within the past 6 months before screening (drinking more than 14 units of alcohol per week \[1 unit ≈ 360 mL of beer or 45 mL of 40% alcohol or 150 mL of wine\]); or positive alcohol breath test at the time of screening or admission. * Patients with poorly controlled hypertension by conventional treatments (systolic blood pressure \[SBP\] ≥ 180 mmHg and/or diastolic blood pressure \[DBP\] ≥ 110 mmHg). * Patients with poorly controlled diabetes (hemoglobin A1c ≥ 9%). * Presence of New York Heart Association (NYHA) class III-IV heart failure, left ventricular ejection fraction \< 50%, or prolonged QTc interval (female \> 470 ms, male \> 450 ms) at the time of screening. * Myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, coronary artery bypass grafting, severe deep vein thrombosis or pulmonary embolism within 3 months before screening; poorly controlled severe arrhythmias within the past 3 months before screening, such as poorly controlled recurrent and highly symptomatic ventricular tachycardia, rapid ventricular response atrial fibrillation, or supraventricular tachycardia; or planned cardiac surgery or cardiac revascularization during the main study period. * Cerebrovascular accidents within 6 months before screening; * Known or suspected systemic viral, parasitic, or fungal infections, or active infections requiring expected antibiotic therapy within 14 days after screening. * Human immunodeficiency virus (HIV) antibody positive at screening. * Anticoagulant therapy within 14 days before enrollment (such as warfarin, dabigatran, apixaban). * Patients with bleeding tendency or history of coagulation disorders (such as liver cirrhosis, malignant hematological diseases, antiphospholipid antibody syndrome); * Expected survival time less than 2 years. * History of malignant tumors within the past 5 years (excluding cured skin basal cell carcinoma, skin squamous cell carcinoma, cervical carcinoma in situ, low-grade prostate carcinoma in situ, and cured thyroid basal cell carcinoma). * History of drug abuse within the past 3 years. * Pregnant or lactating women. * Patients with other diseases in the blood system, digestive system, central nervous system, or endocrine system that the investigator believes will interfere with evaluation or limit participation in the trial. * Inability or unwillingness to cooperate or comply with pretreatment medication requirements or study procedures. * Any other condition deemed unsuitable for the clinical trial participation by the investigator.