A Cell-penetrating Helical Polymer For siRNA Delivery to Mammalian Cells
| Autor: | Jianjun Cheng, Lichen Yin, Nathan P. Gabrielson, Hua Lu, Kyung Hoon Kim |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Small interfering RNA
Endosome Cell Cell-Penetrating Peptides 02 engineering and technology Biology Protein Structure Secondary Mice 03 medical and health sciences Drug Discovery medicine Genetics Animals Humans RNA Small Interfering Molecular Biology Cells Cultured 030304 developmental biology Pharmacology 0303 health sciences RNA Transfection 021001 nanoscience & nanotechnology Mice Inbred C57BL Cytosol Membrane medicine.anatomical_structure Biochemistry Biophysics Molecular Medicine Original Article 0210 nano-technology Intracellular HeLa Cells |
| Zdroj: | Molecular Therapy. 20(8):1599-1609 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2012.78 |
| Popis: | Cell-penetrating peptides (CPPs) are routinely used for intracellular delivery of a variety of cargo, including drugs, genes, and short interfering RNA (siRNA). Most CPPs are active only upon exposure to acidic environments inside of late endosomes, thereby facilitating the endosomal escape of internalized vectors. Here, we describe the generation of a synthetic polypeptide--PVBLG(n)-8--that is able to adopt a helical structure independent of pH. Like other CPPs, the helical structure of PVBLG(n)-8 allows the polypeptide to destabilize membranes. However, since the helix is stable at all physiologically relevant pH values between pH 2 and pH 7.4, the membrane permeation properties of PVBLG(n)-8 are irreversible. Given its pH-insensitive activity, our results suggest that PVBLG(n)-8 is able to facilitate efficient siRNA delivery by causing pore formation in the cell membranes through which either free or complexed siRNA is able to diffuse. This nonspecific form of entry into the cell cytosol may prove useful when trying to deliver siRNA to cells which have proven to be difficult to transfect. |
| Databáze: | OpenAIRE |
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