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


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.

SUBMITTER: Link N 

PROVIDER: S-EPMC1356536 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature

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

Link Nils N   Aubel Corinne C   Kelm Jens M JM   Marty René R RR   Greber David D   Djonov Valentin V   Bourhis Jean J   Weber Wilfried W   Fussenegger Martin M  

Nucleic acids research 20060130 2


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 tar  ...[more]

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