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Adv Sci (Weinh). 2018 Dec 5;6(3):1801458. doi: 10.1002/advs.201801458. eCollection 2019 Feb 6.

Peptide-siRNA Supramolecular Particles for Neural Cell Transfection.

Author information

1
Simpson Querrey Institute Northwestern University Chicago IL 60611 USA.
2
Department of Chemistry of Biomacromolecules Institute of Chemistry National Autonomous University of Mexico Ciudad Universitaria Mexico City 04510 Mexico.
3
Department of Pharmacology Feinberg School of Medicine Northwestern University Chicago IL 60611 USA.
4
The Ken & Ruth Davee Department of Neurology & Clinical Neurological Sciences Department of Physiology Feinberg School of Medicine Northwestern University Chicago IL 60611 USA.
5
Department of Chemistry Northwestern University Evanston IL 60208 USA.
6
Department of Materials Science and Engineering Northwestern University Evanston IL 60208 USA.
7
Department of Biomedical Engineering Northwestern University Evanston IL 60208 USA.
8
Department of Medicine Northwestern University Chicago IL 60611 USA.

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

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