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• W2321167350 abstract "Event Abstract Back to Event Nanoparticle-based nonviral delivery of siRNA in zebrafish heart: gene silencing efficiency and siRNA biodistribution Fang Wang1, Lu Gao2, Liuyi Meng1, Jingwei Xiong2 and Ying Luo1 1 Peking university, Biomedical Engineering, China 2 Peking University, Institute of Molecular Medicine, China Introduction: Non-viral nanomaterials hold promise for use as siRNA delivery vectors for treating cardiac diseases. However, the delivery mechanisms of nanomaterials in heart have not been elucidated due to the difficulty to track and image nanoparticles in vivo. Here, we aim to investigate the efficiency, kinetics and distribution of siRNA delivered locally to zebrafish heart through nanomaterials. In particular, the cellular distribution of siRNA was studied via flk:GFP and cmcl2:GFP transgenic zebrafish models in which endothelial cells and cardiomyocytes express GFP, respectively. Materials and Methods: A neutral polyethelenimine (PEI)-based material, PEI-HYD-RGD[1], and a dendrimer-based system, f-PAM4-PEG-R9, were synthesized through coupling reactions[2]. The materials were formulated with siRNA targeting Raldh2 (a retinoic acid-synthesizing enzyme) to form two types of nanoparticles, which were injected intrapleurally to zebrafish models with amputated hearts. The gene silencing effect was evaluated by qPCR. The uptake kinetics and the distribution of CY5-labled siRNA were analyzed via confocal microscopy of cryo-sectioned heart tissues. Results and Discussion: Both delivery systems showed gene silencing effects in zebrafish heart: The expression of Raldh2 was efficiently downregulated by about 50% and 80% via the PEI-HYD-RGD and f-PAM4-PEG-R9 vectors, respectively, compared to the models injected with DPBS only (Fig.1). In the f-PAM4-PEG-R9 system, the uptake of siNC-CY5 by the injured heart tissue began at 3 h after injection, reached the highest level in heart at 6 h and decreased at 24 h (Fig 2A-C). In the transgenic models, nanoparticle mainly located in the injured areas. In the PEI-HYD-RGD-medicated delivery, more nanoparticles were found associated with the cardiomyocytes (Fig 2E) than the endothelial cells (Fig 2D). The results indicate that nanoparticles may preferentially release therapeutic siRNA locally in injured heart tissues and induce differential distribution of siRNA in different cell types. Conclusions: Zebrafish provides a useful model to study the pharmacological mechanisms of siRNA in heart tissue. Nanoparticle-based system can effectively deliver siRNA in heart and may be further studied for optimal gene-silencing efficiency and siRNA distribution in vivo to develop new therapeutics for cardiac diseases. References:[1] Liu J, Zhou J & Luo Y, (2012). Bioconjug Chem, 23(2), 174-183.[2] Liu J, Davis ME and Luo Y et al, (2013). Biomaterials, 34(14), 3729-3736. Keywords: in vivo, siRNA delivery, MYOCARDIAL TISSUE, Non-viral vector Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Enabling RNAi with biomaterials Citation: Wang F, Gao L, Meng L, Xiong J and Luo Y (2016). Nanoparticle-based nonviral delivery of siRNA in zebrafish heart: gene silencing efficiency and siRNA biodistribution. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02978 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Fang Wang Lu Gao Liuyi Meng Jingwei Xiong Ying Luo Google Fang Wang Lu Gao Liuyi Meng Jingwei Xiong Ying Luo Google Scholar Fang Wang Lu Gao Liuyi Meng Jingwei Xiong Ying Luo PubMed Fang Wang Lu Gao Liuyi Meng Jingwei Xiong Ying Luo Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page." @default.
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• W2321167350 title "Nanoparticle-based nonviral delivery of siRNA in zebrafish heart: gene silencing efficiency and siRNA biodistribution" @default.
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