Mutants of listeriolysin O for enhanced liposomal delivery of macromolecules.

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.

journal_name

J Biotechnol

journal_title

Journal of biotechnology

authors

Walls ZF,Goodell S,Andrews CD,Mathis J,Lee KD

doi

10.1016/j.jbiotec.2013.01.029

subject

Has Abstract

pub_date

2013-04-15 00:00:00

pages

500-2

issue

4

eissn

0168-1656

issn

1873-4863

pii

S0168-1656(13)00065-5

journal_volume

164

pub_type

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