Kim, Dongkyu Ku, Sook Hee Kim, Hyosuk Jeong, Ji Hoon Lee, Minhyung Kwon, Ick Chan Choi, Donghoon Kim, Sun Hwa 2024-01-20T02:33:46Z 2024-01-20T02:33:46Z 2021-09-05 2016-12-10 0168-3659 https://pubs.kist.re.kr/handle/201004/123322 Gene therapy is aimed at selectively knocking up or knocking down the target genes involved in the development of diseases. In many human diseases, dysregulation of disease-associated genes is occurred concurrently: some genes are abnormally turned up and some are turned down. In the field of non-viral gene therapy, plasmid DNA (pDNA) and small interfering RNA (siRNA) are suggested as representative regulation tools for activating and silencing the expression of genes of interest, representatively. Herein, we simultaneously loaded both siRNA (Src homology region 2 domain-containing tyrosine phosphatase-1 siRNA, siSHP-1) for anti-apoptosis and pDNA (hypoxia-inducible vascular endothelial growth factor expression vector, pHI-VEGF) for angiogenesis in a single polymeric nanocarrier and used to synergistically attenuate ischemia-reperfusion (IR)-induced myocardial infarction, which is mainly caused by dysregulating of cardiac apoptosis and angiogenesis. For dual-modality cardiac gene delivery, siSHP-1 and pHI-VEGF were sequentially incorporated into a stable nanocomplex by using deoxycholic acid-modified polyethylenimine (DA-PEI). The resulting DA-PEI/siSHP-1/pHI-VEGF complexes exhibited the high structural stability against polyanion competition and the improved resistance to digestion by nucleases. The cardiac administration of DA-PEI/siSHP-1/pHI-VEGF reduced cardiomyocyte apoptosis and enhanced cardiac microvessel formation, thereby reducing infarct size in rat ischemia-reperfusion model. The simultaneous anti-apoptotic and angiogenic gene therapies synergized the cardioprotective effects of each strategy; thus our dual-modal single-carrier gene delivery system can be considered as a promising candidate for treating ischemic heart diseases. (C) 2016 Elsevier B.V. All rights reserved. English ELSEVIER RECEPTOR-INDUCED APOPTOSIS LOW-MOLECULAR-WEIGHT PLASMID DNA DOMAIN DEATH POLYETHYLENIMINE EFFICIENCY PROTEIN VECTOR MODEL Simultaneous regulation of apoptotic gene silencing and angiogenic gene expression for myocardial infarction therapy: Single-carrier delivery of SHP-1 siRNA and VEGF-expressing pDNA Article 10.1016/j.jconrel.2016.10.017 1 JOURNAL OF CONTROLLED RELEASE, v.243, pp.182 - 194 JOURNAL OF CONTROLLED RELEASE 243 182 194 scie scopus 000392290000016 2-s2.0-84993982634 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article RECEPTOR-INDUCED APOPTOSIS LOW-MOLECULAR-WEIGHT PLASMID DNA DOMAIN DEATH POLYETHYLENIMINE EFFICIENCY PROTEIN VECTOR MODEL SHP-1 siRNA VEGF plasmid DNA Myocardial ischemia-reperfusion injury Deoxycholic acid-modified polyethylenimine