Intracellular Nucleic Acid Delivery by the Supercharged Dengue Virus Capsid Protein

被引:34
作者
Freire, Joao Miguel [1 ]
Veiga, Ana Salome [1 ]
Conceicao, Thais M. [2 ]
Kowalczyk, Wioleta [3 ]
Mohana-Borges, Ronaldo [4 ]
Andreu, David [3 ]
Santos, Nuno C. [1 ]
Da Poian, Andrea T. [2 ]
Castanho, Miguel A. R. B. [1 ]
机构
[1] Univ Lisbon, Inst Med Mol, Fac Med, P-1699 Lisbon, Portugal
[2] Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil
[3] Pompeu Fabra Univ, Dept Expt & Hlth Sci, Barcelona, Spain
[4] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio De Janeiro, Brazil
来源
PLOS ONE | 2013年 / 8卷 / 12期
关键词
CELL-PENETRATING PEPTIDES; FUNCTIONAL PROTEINS; LIPID-COMPOSITION; DRUG-DELIVERY; IN-VITRO; EFFICACY; BINDING; VECTOR; DRIVEN; NMR;
D O I
10.1371/journal.pone.0081450
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Supercharged proteins are a recently identified class of proteins that have the ability to efficiently deliver functional macromolecules into mammalian cells. They were first developed as bioengineering products, but were later found in the human proteome. In this work, we show that this class of proteins with unusually high net positive charge is frequently found among viral structural proteins, more specifically among capsid proteins. In particular, the capsid proteins of viruses from the Flaviviridae family have all a very high net charge to molecular weight ratio (> + 1.07/kDa), thus qualifying as supercharged proteins. This ubiquity raises the hypothesis that supercharged viral capsid proteins may have biological roles that arise from an intrinsic ability to penetrate cells. Dengue virus capsid protein was selected for a detailed experimental analysis. We showed that this protein is able to deliver functional nucleic acids into mammalian cells. The same result was obtained with two isolated domains of this protein, one of them being able to translocate lipid bilayers independently of endocytic routes. Nucleic acids such as siRNA and plasmids were delivered fully functional into cells. The results raise the possibility that the ability to penetrate cells is part of the native biological functions of some viral capsid proteins.
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页数:10
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