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可还原聚(寡聚精氨酸)作为血管内皮生长因子表达的基因载体在心脏中的应用。

Cardiac Usage of Reducible Poly(oligo-D-arginine) As a Gene Carrier for Vascular Endothelial Growth Factor Expression.

机构信息

Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, South Korea.

Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.

出版信息

PLoS One. 2015 Dec 9;10(12):e0144491. doi: 10.1371/journal.pone.0144491. eCollection 2015.

Abstract

Developments of non-viral carriers have headed toward reducing cytotoxicity, which results from the use of conventional gene carriers, and enhancing gene delivery efficiency. Cys-(d-R9)-Cys repeated reducible poly(oligo-D-arginine) (rPOA) is one of the most efficient non-viral carriers for gene therapy; however, while its efficiency has been verified in the lung and brain, it is necessary to confirm its activity in each organ or tissue since there are differences of gene carrier susceptibility to among tissue types. We therefore tested the compatibility of rPOA in cardiac tissue by in vitro or in vivo experiments and confirmed its high transfection efficiency and low cytotoxicity. Moreover, substantial regenerative effects were observed following transfection with rPOA/pVEGF expression vector complexes (79% decreased infarct size) compared to polyethyleneimine (PEI) (34% decreased infarct size) in a rat myocardial infarction (MI) model. These findings suggest that rPOA efficiently enables DNA transfection in cardiac tissue and can be used as a useful non-viral therapeutic gene carrier for gene therapy in ischemic heart disease.

摘要

非病毒载体的发展方向是降低细胞毒性,这是由于传统基因载体的使用,以及提高基因传递效率。半胱氨酸-(d-R9)-半胱氨酸重复还原聚(寡-D-精氨酸)(rPOA)是基因治疗中最有效的非病毒载体之一;然而,虽然它在肺部和大脑中的效率已经得到验证,但有必要确认其在每个器官或组织中的活性,因为组织类型对基因载体的敏感性存在差异。因此,我们通过体外或体内实验测试了 rPOA 在心脏组织中的相容性,并证实了其具有高转染效率和低细胞毒性。此外,与聚乙烯亚胺(PEI)(梗死面积减少 34%)相比,rPOA/pVEGF 表达载体复合物转染后在大鼠心肌梗死(MI)模型中观察到显著的再生效果(梗死面积减少 79%)。这些发现表明,rPOA 可有效地将 DNA 转染到心脏组织中,并可作为缺血性心脏病基因治疗的有用非病毒治疗基因载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edd/4674056/c31b913ef753/pone.0144491.g001.jpg

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