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

Link, Nils; Aubel, Corinne; Kelm, Jens M; Marty, René R; Greber, David; Djonov, Valentin; Bourhis, Jean; Weber, Wilfried; Fussenegger, Martin (2006). Therapeutic protein transduction of mammalian cells and mice by nucleic acid-free lentiviral nanoparticles. Nucleic acids research, 34(2), e16. London: Oxford University Press 10.1093/nar/gnj014

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Djonov, Valentin

ISSN:

0305-1048

ISBN:

16449199

Publisher:

Oxford University Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:49

Last Modified:

25 Oct 2019 21:47

Publisher DOI:

10.1093/nar/gnj014

PubMed ID:

16449199

Web of Science ID:

000235291300009

BORIS DOI:

10.7892/boris.20357

URI:

https://boris.unibe.ch/id/eprint/20357 (FactScience: 3645)

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