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Proprotein convertase subtilisin/kexin type 9: A new target molecule for gene therapy

Cellular & Molecular Biology Letters volume 17, pages 228–239 (2012)Cite this article

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel target for controlling plasma levels of low-density lipoprotein cholesterol (LDL-C) and decreasing the risk of cardiovascular diseases. At present it is clear that the major classes of commonly prescribed lipid-lowering medications increase serum PCSK9 levels and fail to protect a significant percentage of patients from cardiovascular events. Therefore development of new LDL-C lowering medications that either do not increase circulating PCSK9 levels or work through inhibition of PCSK9 expression and protease activity is a highly desirable approach to overcome hypercholesterolemia. Since there are several agents which are being evaluated in human preclinical and clinical trials, this review summarizes current therapeutic strategies targeting PCSK9, including specific antibodies, antisense oligonucleotides, small interfering RNAs (siRNAs) and other small-molecule inhibitors.

Abbreviations

ApoER2:

apolipoprotein E receptor 2

ASO:

oligonucleotide inhibitors

CHD:

coronary heart disease

dsRNA:

double-stranded ribonucleic acid

EGF-A:

epidermal growth factor-like repeat

GOF:

gain of function

HDL-C:

highdensity lipoprotein cholesterol

HNF1:

hepatocyte nuclear factor 1

LDL-C:

low-density lipoprotein cholesterol

LDLR:

low-density lipoprotein receptor

LOF:

loss of function

mVLDLR:

mouse very low-density lipoprotein receptor

PCSK9:

proprotein convertase subtilisin kexin type 9

PPARα:

peroxisome proliferator activated receptor alpha

RISC:

RNA-induced silencing complex

RNAi:

RNA interference

siRNA:

small interfering RNA

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Authors and Affiliations

  1. Department of Animal Physiology and Development, Adam Mickiewicz University, 89 Umultowska St., 61-614, Poznan, Poland

    Anna Banaszewska, Michal Piechota & Robert Plewa

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  1. Anna Banaszewska
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  2. Michal Piechota
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  3. Robert Plewa
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Correspondence to Robert Plewa.

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Banaszewska, A., Piechota, M. & Plewa, R. Proprotein convertase subtilisin/kexin type 9: A new target molecule for gene therapy. Cell Mol Biol Lett 17, 228–239 (2012). https://doi.org/10.2478/s11658-012-0006-7

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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