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Title

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

 

Authors

Bhooma Vijayaraghavan1, Kavitha Danabal2, Giri Padmanabhan1, Kumaresan Ramanathan3*

 

Affiliation

1Kidney Care, C50, 10TH B Cross, East Thillai Nagar, Tiruchirappalli-620 018, India;

2Department of Botany & Microbiology, AVVM Sri Puspam College (Autonomous), Poondi, Thanjavur, India;

3Department of Medical Biochemistry, Division of Biomedical Sciences, School of Medicine, College of Health Sciences, Mekelle University (Ayder Campus), Mekelle, Ethiopia;

 

Email

kumaresanramanatha@gmail.com; kumaresan.ramanathas@mu.edu.et;

 

Article Type

Hypothesis

 

Date

Received April 19, 2018; Revised May 5, 2018; Accepted May 30, 2018; Published May 31, 2018

 

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.

 

Keywords

PCSK9 mRNA, siRNA, LDL, free energy of hybridization, knock down

 

Citation

Vijayaraghavan et al. Bioinformation 14(5): 248-251 (2018)

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.