Therapeutic protein transduction of mammalian cells and mice by nucleic acid-free lentiviral nanoparticles.

Details

Serval ID
serval:BIB_9DA94534ECE8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Therapeutic protein transduction of mammalian cells and mice by nucleic acid-free lentiviral nanoparticles.
Journal
Nucleic Acids Research
Author(s)
Link N., Aubel C., Kelm J.M., Marty R.R., Greber D., Djonov V., Bourhis J., Weber W., Fussenegger M.
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
34
Number
2
Pages
e16
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Abstract
The straightforward production and dose-controlled administration of protein therapeutics remain major challenges for the biopharmaceutical manufacturing and gene therapy communities. Transgenes linked to HIV-1-derived vpr and pol-based protease cleavage (PC) sequences were co-produced as chimeric fusion proteins in a lentivirus production setting, encapsidated and processed to fusion peptide-free native protein in pseudotyped lentivirions for intracellular delivery and therapeutic action in target cells. Devoid of viral genome sequences, protein-transducing nanoparticles (PTNs) enabled transient and dose-dependent delivery of therapeutic proteins at functional quantities into a variety of mammalian cells in the absence of host chromosome modifications. PTNs delivering Manihot esculenta linamarase into rodent or human, tumor cell lines and spheroids mediated hydrolysis of the innocuous natural prodrug linamarin to cyanide and resulted in efficient cell killing. Following linamarin injection into nude mice, linamarase-transducing nanoparticles impacted solid tumor development through the bystander effect of cyanide.
Keywords
Animals, Antineoplastic Agents/metabolism, Cell Line, Cell Line, Tumor, Combined Modality Therapy, Cricetinae, Genetic Therapy/methods, Genetic Vectors, Humans, Lentivirus/genetics, Mice, Mice, Nude, Nanostructures, Neoplasms/drug therapy, Neoplasms/therapy, Nitriles/therapeutic use, Prodrugs/therapeutic use, Protein Transport, Recombinant Fusion Proteins/metabolism, Spheroids, Cellular, Transfection, beta-Glucosidase/genetics, beta-Glucosidase/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
01/12/2014 17:37
Last modification date
20/08/2019 15:04
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