Peptide-siRNA Supramolecular Particles for Neural Cell Transfection.
Armando Hernández GarciaZaida ÁlvarezDina SimkinAshwin MadhanEloise ParisetFaifan TantakittiOscar de J Vargas-DorantesSungsoo S LeeEvangelos KiskinisSamuel I StuppPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2018)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- cancer therapy
- genome wide
- single cell
- amino acid
- copy number
- endoplasmic reticulum stress
- binding protein
- cell therapy
- high throughput
- spinal cord
- water soluble
- signaling pathway
- energy transfer
- dna methylation
- transcription factor
- brain injury
- high resolution
- mesenchymal stem cells
- quantum dots
- liquid chromatography