Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans |
| |
Authors: | Nascimento Fábio Dupart Hayashi Mirian A F Kerkis Alexandre Oliveira Vitor Oliveira Eduardo B Rádis-Baptista Gandhi Nader Helena Bonciani Yamane Tetsuo Tersariol Ivarne Luis dos Santos Kerkis Irina |
| |
Institution: | Departamento de Bioquímica, Universidade Federal de S?o Paulo-Escola Paulista de Medicina, Rua 3 de Maio, 100, Ed. INFAR, CEP 04044-020, S?o Paulo, Brazil. |
| |
Abstract: | Recently we have shown that crotamine, a toxin from the South American rattlesnake Crotalus durissus terrificus venom, belongs to the family of cell-penetrating peptides. Moreover, crotamine was demonstrated to be a marker of centrioles, of cell cycle, and of actively proliferating cells. Herein we show that this toxin at non-toxic concentrations is also capable of binding electrostatically to plasmid DNA forming DNA-peptide complexes whose stabilities overcome the need for chemical conjugation for carrying nucleic acids into cells. Interestingly, crotamine demonstrates cell specificity and targeted delivery of plasmid DNA into actively proliferating cells both in vitro and in vivo, which distinguishes crotamine from other known natural cell-penetrating peptides. The mechanism of crotamine penetration and cargo delivery into cells was also investigated, showing the involvement of heparan sulfate proteoglycans in the uptake phase, which is followed by endocytosis and peptide accumulation within the acidic endosomal vesicles. Finally, the permeabilization of endosomal membranes induced by crotamine results in the leakage of the vesicles contents to the cell cytosol. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|