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

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.