Non-viral gene delivery of the oncotoxic protein NS1 for treatment of hepatocellular carcinoma.

Animals Carcinoma, Hepatocellular / therapy Genetic Therapy Liver Neoplasms / therapy Mice Plasmids Proteins
Gene therapy Hepatocellular carcinoma Nanoparticles Oncotoxic protein Parvovirus

Journal

Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908

Informations de publication

Date de publication:
10 06 2021
Historique:
received: 28 07 2020
revised: 10 04 2021
accepted: 20 04 2021
pubmed: 25 4 2021
medline: 8 7 2021
entrez: 24 4 2021
Statut: ppublish

Résumé

Hepatocellular carcinoma (HCC) is related to increasing incidence rates and poor clinical outcomes due to lack of efficient treatment options and emerging resistance mechanisms. The aim of the present study is to exploit a non-viral gene therapy enabling the expression of the parvovirus-derived oncotoxic protein NS1 in HCC. This anticancer protein interacts with different cellular kinases mediating a multimodal host-cell death. Lipoplexes (LPX) designed to deliver a DNA expression plasmid encoding NS1 are characterized using a comprehensive set of in vitro assays. The mechanisms of cell death induction are assessed and phosphoinositide-dependent kinase 1 (PDK1) is identified as a potential predictive biomarker for a NS1-LPX-based gene therapy. In an HCC xenograft mouse model, NS1-LPX therapeutic approach results in a significant reduction in tumor growth and extended survival. Data provide convincing evidence for future studies using a targeted NS1 gene therapy for PDK1 overexpressing HCC.

Identifiants

DOI: 10.1016/j.jconrel.2021.04.023 PMID: 33894304
pubmed: 33894304
pii: S0168-3659(21)00189-9
doi: 10.1016/j.jconrel.2021.04.023
pii:
doi:

Substances chimiques

Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

138-152

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Auteurs

Dominik Witzigmann (D)

Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland; Department of Biochemistry and Molecular Biology, University of British Columbia, Health Sciences Mall, V6T 1Z3 Vancouver, British Columbia, Canada.

Philip Grossen (P)

Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland.

Cristina Quintavalle (C)

Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, 4003 Basel, Switzerland.

Manuela Lanzafame (M)

Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, 4003 Basel, Switzerland.

Susanne H Schenk (SH)

Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland.

Xue-Ting Tran (XT)

Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland.

Bernhard Englinger (B)

Applied and Experimental Oncology, Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.

Patrick Hauswirth (P)

Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland.

David Grünig (D)

Division of Clinical Pharmacology and Toxicology, University Hospital of Basel, 4031 Basel, Switzerland.

Sushilla van Schoonhoven (S)

Applied and Experimental Oncology, Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.

Stephan Krähenbühl (S)

Division of Clinical Pharmacology and Toxicology, University Hospital of Basel, 4031 Basel, Switzerland.

Luigi M Terracciano (LM)

Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, 4003 Basel, Switzerland.

Walter Berger (W)

Applied and Experimental Oncology, Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.

Salvatore Piscuoglio (S)

Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, 4003 Basel, Switzerland; Visceral Surgery laboratory, Clarunis, Department of Biomedicine, 4031 Basel, Switzerland.

Luca Quagliata (L)

Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, 4003 Basel, Switzerland.

Jean Rommelaere (J)

Infection, Inflammation and Cancer Program, Division of Tumor Virology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

Jürg P F Nüesch (JPF)

Infection, Inflammation and Cancer Program, Division of Tumor Virology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

Jörg Huwyler (J)

Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland. Electronic address: joerg.huwyler@unibas.ch.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Non-viral gene delivery of the oncotoxic...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Carcinome hépatocellulaire › Non-viral gene delivery of the oncotoxic...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Thérapie génétique › Non-viral gene delivery of the oncotoxic...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Non-viral gene delivery of the oncotoxic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Non-viral gene delivery of the oncotoxic...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Plasmides › Non-viral gene delivery of the oncotoxic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Non-viral gene delivery of the oncotoxic...