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

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
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

ribonucleic acids
RNA
Transfection
genes
Peptides
peptides
Genes
proteins
cells
Proteins
Screening
screening
Gene Knockdown Techniques
Synaptophysin
Solid-Phase Synthesis Techniques
Genetic Association Studies
Cytotoxicity
Cell- and Tissue-Based Therapy
activity (biology)
assembling

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

Cite this

Hernandez-Garcia, A., Álvarez, Z., Simkin, D., Madhan, A., Pariset, E., Tantakitti, F., ... Stupp, S. I. (Accepted/In press). Peptide–siRNA Supramolecular Particles for Neural Cell Transfection. Advanced Science, [1801458]. https://doi.org/10.1002/advs.201801458

Peptide–siRNA Supramolecular Particles for Neural Cell Transfection. / Hernandez-Garcia, Armando; Álvarez, Zaida; Simkin, Dina; Madhan, Ashwin; Pariset, Eloise; Tantakitti, Faifan; de J. Vargas-Dorantes, Oscar; Lee, Sungsoo S.; Kiskinis, Evangelos; Stupp, Samuel I.

In: Advanced Science, 01.01.2018.

Research output: Contribution to journalArticle

Hernandez-Garcia, A, Álvarez, Z, Simkin, D, Madhan, A, Pariset, E, Tantakitti, F, de J. Vargas-Dorantes, O, Lee, SS, Kiskinis, E & Stupp, SI 2018, 'Peptide–siRNA Supramolecular Particles for Neural Cell Transfection', Advanced Science. https://doi.org/10.1002/advs.201801458
Hernandez-Garcia A, Álvarez Z, Simkin D, Madhan A, Pariset E, Tantakitti F et al. Peptide–siRNA Supramolecular Particles for Neural Cell Transfection. Advanced Science. 2018 Jan 1. 1801458. https://doi.org/10.1002/advs.201801458
Hernandez-Garcia, Armando ; Álvarez, Zaida ; Simkin, Dina ; Madhan, Ashwin ; Pariset, Eloise ; Tantakitti, Faifan ; de J. Vargas-Dorantes, Oscar ; Lee, Sungsoo S. ; Kiskinis, Evangelos ; Stupp, Samuel I. / Peptide–siRNA Supramolecular Particles for Neural Cell Transfection. In: Advanced Science. 2018.
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