Study on Regulation of Low Density Lipoprotein Cholesterol Metabolism using PCSK9 Gene Silencing: A computational Approach

Abstract

Combating and preventing abnormality in lipid metabolism becomes a pivotal criterion for research. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein; it promotes the degradation of low-density lipoprotein receptors (LDL-R) and hence increases LDL-C levels. Silencing the gene PCSK9 at post-transcriptional level with the help of small interfering Ribo nucleic acid (siRNA) gives a new insight and a novel therapeutic way to regulate LDL-C metabolism. Designing and selecting an efficient siRNA for silencing PCSK9 at post transcriptional level through computational approach. We have designed three siRNAs to silence each mRNA of PCSK9 through computational analysis using software Invivogen. Their minimum free energy of hybridization along with their secondary structure was obtained using bioinformatics tool BIBISERV2-RNAHYBRID. Further factors like GC content, structural linearity and h-b index of mRNA-siRNA complex was calculated to assess their knockdown efficiency. The minimum free energy of hybridization of the three designed siRNA1, siRNA2 and siRNA3 for target mRNA is as follows-27.1kcal/mol,-25.7kcal/mol and-28.8 kcal/mol. siRNA1 having the least minimum free energy of hybridization i.e.-27.1 kcal/mol are predicted to be the most efficient towards the PCSK9 gene silencing. Background: Amid the previous couple of years, the proprotein convertase subtilisinkexin 9 (PCSK9) field has been scorching, powered by the acknowledgment that PCSK9 is a key player in plasma cholesterol digestion system and by a trust, shared by researchers in the educated community and industry alike, that PCSK9 is an objective for treating hypercholesterolemia. PCSK9 directs the levels of the LDL receptor [1-3], which is a plasma membrane glycoprotein that expels cholesterol rich LDL particles from the plasma [4, 5]. PCSK9 is an individual from the mammalian serine proprotein convertase family that commonly capacities in the proteolytic handling and development of secretory proteins [6, 7]. PCSK9 was the principal relative to be embroiled in an overwhelmingly acquired type of hypercholesterolemia [8]. The human hereditary and quality expression disclosures started enthusiasm for characterizing PCSK9 capacity. Mice trial