Inclusion Criteria:
1. Male or female aged 18 to 60 years (inclusive).
2. Subjects with essential hypertension who are either treatment-naive or have remained off any antihypertensive medication for ≥ 30 days prior to screening and in whom the investigator deems no additional antihypertensive therapy necessary during the study period.
3. Body-mass index (BMI) 18.6-30kg/m² (inclusive); body weight ≥ 50 kg for men and ≥ 45 kg for women.
4. Has maintained a stable diet for at least 4 weeks before screening and has no plan to make a clinically significant change in diet or body weight during the study (a change \> 10 % is considered significant).
5. Agrees to use a highly effective method of contraception and to avoid becoming a parent from enrollment until 12 months after the last dose.
6. Able to understand the study requirements, willing to comply, and provides written informed consent.
Phase I subjects must simultaneously meet the following criteria:
7. At screening and within 24 h before randomization, the 24-h ambulatory blood-pressure monitoring shows mean systolic blood pressure (SBP) \> 130 mmHg and \< 150 mmHg.
8. At screening and baseline, fasting serum LDL-C is ≥ 100 mg/dL (2.6 mmol/L) and \< 190 mg/dL (4.9 mmol/L) in subjects who are either lipid-lowering-therapy-naive or have not received any lipid-lowering drug within 30 days before screening and whom the investigator judges will not require any additional lipid-lowering therapy during the study.
Phase II subjects must simultaneously meet the following criteria:
9. At screening and within 24h before randomization, 24-h ambulatory blood-pressure monitoring must show mean SBP \> 130 mmHg and \< 160 mmHg.
10. At screening and baseline, fasting serum LDL-C ≥ 100 mg/dL (2.6 mmol/L). Subjects already on statin therapy must have been on a stable statin dose and regimen for at least 30 days prior to screening and must have no planned changes to their statin treatment during the study.
Exclusion Criteria:
1. Any history of severe illness-apart from hypertension and hyperlipidemia-that in the investigator's opinion could influence trial outcomes, including but not limited to diseases of the circulatory system (e.g., orthostatic hypotension, NYHA class II-IV heart failure, aortic stenosis, major aortic aneurysm or dissection, hypertensive encephalopathy, acute stroke, transient ischemic attack, acute myocardial infarction, significant arrhythmias), endocrine, neurologic, gastrointestinal, genitourinary, hematologic, immunologic, psychiatric, or metabolic disorders.
2. History of allergic disease or atopic diathesis (≥3 drug or food allergies), or known hypersensitivity to oligonucleotide-based therapeutics.
3. Use of anti-PCSK9 or anti-AGT antibody agents within 6 months before screening, or of PCSK9- or AGT-targeted oligonucleotide drugs within 12 months before screening.
4. Malignancy within 5 years before informed-consent signature (exceptions: adequately resected and cured basal- or squamous-cell skin carcinoma, cervical carcinoma in situ, or other cancers considered cured by surgery alone).
5. Left-ventricular ejection fraction (LVEF) \< 40% at screening; or significant aortic or peripheral vascular disease, or any vascular condition requiring surgical intervention.
6. Type 1 diabetes, or type 2 diabetes with inadequate glycaemic control (HbA1c ≥ 8%).
7. Major surgery within 6 months before dosing, or planned major surgery during the study period.
8. Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m² (by simplified MDRD equation) or urine albumin-to-creatinine ratio (UACR) \> 300 mg/g at screening.
9. At screening, any of the following laboratory abnormalities: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin(TBIL),gamma-glutamyl transferase(GGT), or alkaline phosphatase(ALP) \> 1.5 × upper limit of normal (ULN), or serum potassium \> 5.5 mmol/L (one repeat measurement permitted).
10. Mean 24-h ambulatory diastolic blood pressure (DBP) \> 110 mmHg at screening and/or within 24 h prior to randomization (one repeat measurement permitted).
11. QT/QTc prolongation at screening or baseline: QT interval corrected by Fridericia's formula (QTcF)≥ 450 ms (men) or ≥ 460 ms (women).
12. Positive serology for HBsAg, anti-hepatitis C virus(HCV), HCV core antigen, anti-human immunodeficiency virus (HIV), or Treponema pallidum antibody; if Treponema pallidum antibody is positive, a confirmatory rapid plasma reagin(RPR) test is required and must also be positive.
13. Known or suspected secondary hypertension, including but not limited to bilateral renal-artery stenosis, primary aldosteronism, pheochromocytoma, polycystic kidney disease, or drug-induced hypertension.
14. Occupations involving hazardous operations such as piloting vessels or working at height.
15. Subcutaneous-injection intolerance, or prominent abdominal scarring, tattoos, or other conditions that could materially interfere with study-drug administration or the assessment of local tolerability.
16. Blood loss or donation \> 400 mL within 3 months before dosing (menstrual bleeding excluded) and/or platelet donation within 2 weeks.
17. Use, within 28 days before dosing, of any drug, nutraceutical, vitamin, or dietary supplement known to affect lipid metabolism.
18. History of drug abuse or positive urine drug screen, and/or use of illicit drugs within 3 months before screening, and/or habitual use of any psychoactive substance (including herbal preparations).
19. Average daily consumption \> 5 cigarettes (or equivalent e-cigarette use) within 3 months before screening and/or unwillingness to abstain from all tobacco products during the study.
20. Regular alcohol consumption within 6 months before screening (i.e., \> 14 units/week; 1 unit = 360 mL of 5% beer, 45 mL of 40% spirits, or 150 mL of 12% wine) and inability to comply with alcohol-restriction requirements during the study.
21. Daily intake of excessive tea, coffee, and/or caffeine-containing beverages (≥ 8 cups/day; 1 cup = 250 mL) within 1 month before screening.
22. Participation in any clinical trial within 3 months before screening (12 months for oligonucleotide investigational drugs).
23. Subjects who, for any other reason, are unlikely to complete the study or whom the investigator deems should not be enrolled.
24. Pregnant or lactating women.
25. History of syncope within 3 months before screening.
26. Receipt of a live vaccine within 4 weeks before screening or planned live-vaccine administration during the study.
27. Use of long-acting estrogen and/or progestin injections or implants within 6 months before dosing.
28. Women of child-bearing potential who engaged in unprotected intercourse with a partner within 28 days before dosing.
