Apoliprotein C-III (Apo C-III) inhibitors effect of antisense oligonucleotides in the management of dyslipidemia

Abstract

Introduction: Dyslipidemia is an abnormal condition of blood lipid levels with a global prevalence of 31.2% which can cause various complications including atherosclerosis that can develop into stroke. Therefore, it is necessary to develop therapeutic modalities. One of them is Antisense Oligonucleotides (ASO) which target Apo C-III, a protein that controls body fat metabolism. Purpose: This study aims to summarize the current progress, challenges, and potency of the apoliprotein C-III (Apo C-III) inhibitors effect of antisense oligonucleotides in the management of dyslipidemia Methods: This paper is a literature review that collects and selects data from credible sources using the keywords apoliprotein C-III, antisense oligonucleotides, and dyslipidemia Results: Antisense Oligonucleotides have high specificity and efficiency in inhibiting Apo C-III. Administration of ASO significantly reduced Apo C-III mRNA up to 98% and Apo C-III plasma protein up to 65% in experimental animals and reduced triglycerides up to 70.9% in clinical trials. A decrease in very low density lipoprotein (VLDL) of up to 69.2% was identified in the administration of ISIS 304801, spesific ASO in humans. The administration of ISIS 304801 also reduced the number of chylomicron particles as a source of cholesterol up to 61.1% and significantly increased the number of high-density lipoprotein (HDL) up to 45.7%, which represented the role of the modality as atheroprotection. Over time, an increase in the endosomal release, distribution, and half-life of ASO was achieved by modification of phosphorothioate linkages and lipid conjugation which represented an increase in ASO concentration. It also facilitates the interaction between ASO and intracellular spesific Apo C-III coding mRNA Conclusion: Antisense oligonucleotides have great potential to inhibit Apo C-III as a treatment for dyslipidemia.