@article{f7d0910c80734ed5b5755b98b103d5e0,
title = "Peptide–siRNA Supramolecular Particles for Neural Cell Transfection",
abstract = "Small interfering ribonucleic acid (siRNA)-based gene knockdown is an effective tool for gene screening and therapeutics. However, the use of nonviral methods has remained an enormous challenge in neural cells. A strategy is reported to design artificial noncationic modular peptides with amplified affinity for siRNA via supramolecular assembly that shows efficient protein knockdown in neural cells. By solid phase synthesis, a sequence that binds specifically double-stranded ribonucleic acid (dsRNA) with a self-assembling peptide for particle formation is integrated. These supramolecular particles can be further functionalized with bioactive sequences without affecting their biophysical properties. The peptide carrier is found to silence efficiently up to 83% of protein expression in primary astroglial and neuronal cell cultures without cytotoxicity. In the case of neurons, a reduction in electrical activity is observed once the presynaptic protein synaptophysin is downregulated by the siRNA–peptide particles. The results demonstrate that the supramolecular particles offer an siRNA delivery platform for efficient nonviral gene screening and discovery of novel therapies for neural cells.",
keywords = "glial cells, glial fibrillary acidic protein (GFAP), knockdown, neurons, protein engineering, supramolecular particles, synaptophysin, transfection",
author = "Armando Hernandez-Garcia and Zaida {\'A}lvarez and Dina Simkin and Ashwin Madhan and Eloise Pariset and Faifan Tantakitti and {de J. Vargas-Dorantes}, Oscar and Lee, {Sungsoo S.} and Evangelos Kiskinis and Stupp, {Samuel I.}",
note = "Funding Information: A.H.-G. and Z.A. contributed equally to this work. This work was supported by National Institutes of Health/ National Institute of Biomedical Imaging and Bioengineering Award Number 5R01EB003806-07 and by the Center for Regenerative Nanomedicine at the Simpson Querrey Institute at Northwestern. The EK lab is supported by research grants from the Les Turner ALS Foundation, the Muscular Dystrophy Association, Target ALS and Dravet Foundation. A.H.-G. received postdoctoral support from the Latin American Fellowship PEW Charitable Trusts. Z.A. received postdoctoral support from the Beatriu de Pin{\'o}s Fellowship 2014 BP-A 00007 (Ag{\`e}ncia de Gesti{\'o} d{\textquoteright}Ajust Universitaris i de Recerca, AGAUR) and the PVA Grant # PVA17_RF_0008 from the Paralyzed Veterans of America (PVA) Research Foundation. This work was supported by the following core facilities of Northwestern University: the Peptide Synthesis Core and the Analytical Bionanotechnology Equipment Core both at the Simpson Querrey Institute, the Biological Imaging Facility (supported by the Northwestern University Office for Research), the Center for Advanced Microscopy (NCI CCSG P30 CA060553), Keck Biophysics Facility, the SPID facility (NUANCE Center—NSFEEC-0647560), and Flow Cytometry Core (supported by Cancer Center Support Grant NCICA060553). The authors also thank Roya Zandi for technical help, Prof. Liam Palmer for helpful discussions, and Mark Seniw for the schemes of the manuscript. Funding Information: A.H.-G. and Z.A. contributed equally to this work. This work was supported by National Institutes of Health/ National Institute of Biomedical Imaging and Bioengineering Award Number 5R01EB003806-07 and by the Center for Regenerative Nanomedicine at the Simpson Querrey Institute at Northwestern. The EK lab is supported by research grants from the Les Turner ALS Foundation, the Muscular Dystrophy Association, Target ALS and Dravet Foundation. A.H.-G. received postdoctoral support from the Latin American Fellowship PEW Charitable Trusts. Z.A. received postdoctoral support from the Beatriu de Pin?s Fellowship 2014 BP-A 00007 (Ag?ncia de Gesti? d'Ajust Universitaris i de Recerca, AGAUR) and the PVA Grant # PVA17_RF_0008 from the Paralyzed Veterans of America (PVA) Research Foundation. This work was supported by the following core facilities of Northwestern University: the Peptide Synthesis Core and the Analytical Bionanotechnology Equipment Core both at the Simpson Querrey Institute, the Biological Imaging Facility (supported by the Northwestern University Office for Research), the Center for Advanced Microscopy (NCI CCSG P30 CA060553), Keck Biophysics Facility, the SPID facility (NUANCE Center?NSFEEC-0647560), and Flow Cytometry Core (supported by Cancer Center Support Grant NCICA060553). The authors also thank Roya Zandi for technical help, Prof. Liam Palmer for helpful discussions, and Mark Seniw for the schemes of the manuscript. Publisher Copyright: {\textcopyright} 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2019",
month = feb,
day = "6",
doi = "10.1002/advs.201801458",
language = "English (US)",
volume = "6",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley-VCH Verlag",
number = "3",
}