Aptamer Targeting Proprotein Convertase Subtilisin/Kexin Type 9: In Vivo Efficacy in a Hypercholesterolemic Rat Model Publisher

Summary: Could a DNA aptamer help lower cholesterol? In rats with high cholesterol, a PCSK9-targeting aptamer improved LDL and other lipid markers; human trials are still needed. #Cholesterol #Biotech

Milasi Y E ; Sakhaei F ; Palizban A
Source: Research in Pharmaceutical Sciences Published:2026

Abstract

Background and purpose: – Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a key therapeutic target for lowering low-density lipoprotein cholesterol (LDL-C). This study aimed to evaluate the LDL-C-lowering efficacy of a PCSK9-targeting aptamer (AP-1) in a hypercholesterolemic rat model. Experimental approach: – Wistar male rats (n = 48) were divided into 8 groups (n = 6): normal control, negative control, positive control receiving atorvastatin (4 mg/kg body weight) plus ezetimibe (1 mg/kg BW), and a PBS vehicle group. Experimental groups received the aptamer intraperitoneally at 1, 3, and 8 μM;, and one group received 3 μM; aptamer combined with atorvastatin (4 mg/kg BW). Hypercholesterolemia was induced for over 90 days, followed by a 4-week treatment period. Serum lipid parameters, including triglycerides (TG), total cholesterol (T-Chol), LDL-C, and atherogenic indices, were assessed. Findings/Results: – TG, 143.2 ± 16.44 vs. 109 ± 23.05 mg/dL; T-Chol, 88 ± 3.11 vs. 80 ± 7.16 mg/dL, and LDL-C, 19.4 ± 1.12 vs. 14.5 ± 1.56 mg/dL, levels were significantly increased in the hypercholesterolemic rat model compared to the normal group. Treatment with the 3 μM; aptamer produced the most pronounced lipidlowering effects, significantly reducing TG, 95.2 ± 8.76 vs. 143.2 ± 16.44 mg/dL; T-Chol, 61.2 ± 5.11 vs. 88 ± 3.11 mg/dL, and LDL-C, 11.4 ± 0.75 vs. 19.4 ± 1.12 compared to the hypercholesterolemic control group. Furthermore, the atherogenic index of plasma, remnant cholesterol, and Castelli risk index-II were reduced significantly. Conclusion and implications: – AP-1 aptamer-mediated PCSK9 inhibition significantly improved lipid profiles and atherogenic indices, supporting aptamers as a viable alternative to monoclonal antibody-based PCSK9 inhibition. © 2026 Research in Pharmaceutical Sciences