title: MLV based viral-like-particles for delivery of toxic proteins and nuclear transcription factors.
abstract: We have developed nanoparticles based on Murine Leukemia Virus virus-like-particles (VLPs) that efficiently deliver therapeutic bioactive proteins in their native state into target cells. Nuclear transcription factors and toxic proteins were incorporated into the VLPs from stable producer cells without transducing viral-encoded genetic material. Delivery of nuclear transcription factors required incorporation of nuclear export signals (NESs) into the vector backbone for the efficient formation of VLPs. In the presence of an appropriate targeting Env glycoprotein, transcription factors delivered and activated nuclear transcription in the target cells. Additionally, we show delivery of the bacterial toxin, MazF, which is an ACA-specific mRNA interferase resulted in the induction of cell death. The stable producer cells are protected from the toxin through co-expression of the anti-toxin MazE and continuously released MazF incorporating VLPs. This highly adaptable platform can be harnessed to alter and regulate cellular processes by bioactive protein delivery.
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, 675 Hoes Lane Rm 636, Piscataway, NJ, USA.
authors.forename: Dai-Tze
authors.initials: DT
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, 675 Hoes Lane Rm 636, Piscataway, NJ, USA. Electronic address: roth@rwjms.rutgers.edu.
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Roth
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D009052:Leukemia Virus, Murine / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D049790:Nuclear Export Signals; D014157:Transcription Factors / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014161:Transduction, Genetic; D014771:Virion / Q000737:chemistry / Q000235:genetics*
chemical_list: D001427:Bacterial Toxins; D049790:Nuclear Export Signals; D014157:Transcription Factors
keywords: Bacterial toxin; Intracellular delivery; Protein transduction; Transcriptional factors; Viral-like particles