Mutants of listeriolysin O for enhanced liposomal delivery of macromolecules.
J Biotechnol
; 164(4): 500-2, 2013 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-23416330
ABSTRACT
Delivery of macromolecules into the cytosolic space of eukaryotic cells is a pressing challenge in biopharmaceutics. Macromolecules are often encapsulated into liposomes for protection and improved distribution, but the their size often induces endocytosis of the vehicle at the target site, leading to degradation of the cargo. Listeriolysin O is a key virulence factor of Listeria monocytogenes that forms pores in the endosomal membrane, ultimately allowing the bacterium to escape into the cytosol. This function of LLO has been used to improve cytosolic delivery of liposomally encapsulated macromolecules in a number of instances, but its innate toxicity and immunogenicity have prevented it from achieving widespread acceptance. Through site-directed mutagenesis, this study establishes a mutant of LLO (C484S) with enhanced activity, allowing for a reduction in the amount of LLO used for future applications in liposomal drug delivery.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
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Sistemas de Liberação de Medicamentos
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Proteínas de Choque Térmico
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Proteínas Hemolisinas
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Lipossomos
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article