Targeting PCSK9 as a key player in lipid metabolism: exploiting the therapeutic and biosensing potential of aptamers

• Published in: Lipids in health and disease Vol. 23; no. 1; p. 156
• Main Authors: Mahjoubin-Tehran, Maryam, Rezaei, Samaneh, Santos, Raul D, Jamialahmadi, Tannaz, Almahmeed, Wael, Sahebkar, Amirhossein
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.05.2024; BioMed Central; BMC
• Subjects: Analysis; Animals; Aptamer; Aptamers, Nucleotide; Biosensing Techniques - methods; Biosensors; Care and treatment; Diagnosis; DNA sequencing; Dosage and administration; Health aspects; Homeopathy; Humans; Hypercholesterolemia; Hypercholesterolemia - blood; Hypercholesterolemia - diagnosis; Hypercholesterolemia - drug therapy; LDL; LDLR; Lipid Metabolism; Materia medica and therapeutics; Nucleotide sequencing; PCSK9; PCSK9 Inhibitors; Proprotein Convertase 9 - blood; Proprotein Convertase 9 - genetics; Proprotein Convertase 9 - metabolism; Receptors, LDL - metabolism; Review; SELEX Aptamer Technique; Statins; Therapeutics; Iran; PCSK9; Aptamer; Hypercholesterolemia; LDL; LDLR
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-024-02151-8

The degradation of low-density lipoprotein receptor (LDLR) is induced by proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in elevated plasma concentrations of LDL cholesterol. Therefore, inhibiting the interactions between PCSK9 and LDLR is a desirable therapeutic goal for managing hypercholesterolemia. Aptamers, which are RNA or single-stranded DNA sequences, can recognize their targets based on their secondary structure. Aptamers exhibit high selectivity and affinity for binding to target molecules. The systematic evolution of ligands by exponential enrichment (SELEX), a combination of biological approaches, is used to screen most aptamers in vitro. Due to their unique advantages, aptamers have garnered significant interest since their discovery and have found extensive applications in various fields. Aptamers have been increasingly utilized in the development of biosensors for sensitive detection of pathogens, analytes, toxins, drug residues, and malignant cells. Furthermore, similar to monoclonal antibodies, aptamers can serve as therapeutic tools. Unlike certain protein therapeutics, aptamers do not elicit antibody responses, and their modified sugars at the 2'-positions generally prevent toll-like receptor-mediated innate immune responses. The focus of this review is on aptamer-based targeting of PCSK9 and the application of aptamers both as biosensors and therapeutic agents.