Peptide–siRNA Supramolecular Particles for Neural Cell Transfection

Armando Hernandez-Garcia, Zaida Álvarez, Dina Simkin, Ashwin Madhan, Eloise Pariset, Faifan Tantakitti, Oscar de J. Vargas-Dorantes, Sungsoo S. Lee, Evangelos Kiskinis, Samuel I. Stupp

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Article number1801458
JournalAdvanced Science
Volume6
Issue number3
DOIs
Publication statusPublished - Feb 6 2019

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Keywords

  • glial cells
  • glial fibrillary acidic protein (GFAP)
  • knockdown
  • neurons
  • protein engineering
  • supramolecular particles
  • synaptophysin
  • transfection

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Hernandez-Garcia, A., Álvarez, Z., Simkin, D., Madhan, A., Pariset, E., Tantakitti, F., de J. Vargas-Dorantes, O., Lee, S. S., Kiskinis, E., & Stupp, S. I. (2019). Peptide–siRNA Supramolecular Particles for Neural Cell Transfection. Advanced Science, 6(3), [1801458]. https://doi.org/10.1002/advs.201801458