title: Therapeutic Potential of Cell Penetrating Peptides (CPPs) and Cationic Polymers for Chronic Hepatitis B.
abstract: Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. Because current anti-HBV treatments are only virostatic, there is an urgent need for development of alternative antiviral approaches. In this context, cell-penetrating peptides (CPPs) and cationic polymers, such as chitosan (CS), appear of particular interest as nonviral vectors due to their capacity to facilitate cellular delivery of bioactive cargoes including peptide nucleic acids (PNAs) or DNA vaccines. We have investigated the ability of a PNA conjugated to different CPPs to inhibit the replication of duck hepatitis B virus (DHBV), a reference model for human HBV infection. The in vivo administration of PNA-CPP conjugates to neonatal ducklings showed that they reached the liver and inhibited DHBV replication. Interestingly, our results indicated also that a modified CPP (CatLip) alone, in the absence of its PNA cargo, was able to drastically inhibit late stages of DHBV replication. In the mouse model, conjugation of HBV DNA vaccine to modified CS (Man-CS-Phe) improved cellular and humoral responses to plasmid-encoded antigen. Moreover, other systems for gene delivery were investigated including CPP-modified CS and cationic nanoparticles. The results showed that these nonviral vectors considerably increased plasmid DNA uptake and expression. Collectively promising results obtained in preclinical studies suggest the usefulness of these safe delivery systems for the development of novel therapeutics against chronic hepatitis B.
authors.affiliation: Institut National de la Sante et Recherche Medicale (INSERM) U1052, Cancer Research Center of Lyon (CRCL), Lyon 69003, France. ndeboko@yahoo.fr.|Département de Biologie Cellulaire and Moléculaire-Génétique, Faculté de Médecine, Université des Sciences de la Santé, Libreville 241, Gabon. ndeboko@yahoo.fr.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Ndeboko
authors.affiliation: Département de Biologie Cellulaire and Moléculaire-Génétique, Faculté de Médecine, Université des Sciences de la Santé, Libreville 241, Gabon. guylemamy@yahoo.fr.
authors.forename: Guy Joseph
authors.initials: GJ
authors.lastname: Lemamy
authors.affiliation: Department of Cellular and Molecular Medicine, Departement of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, the Panum Institute, University of Copenhagen, Copenhagen DK 2200N, Denmark. ptrn@sund.ku.dk.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Nielsen
authors.affiliation: Institut National de la Sante et Recherche Medicale (INSERM) U1052, Cancer Research Center of Lyon (CRCL), Lyon 69003, France. lucyna.cova@inserm.fr.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Cova
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D001704:Biopolymers / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D057846:Cell-Penetrating Peptides; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers; D017325:Hepatitis B Vaccines / Q000008:administration & dosage; D015611:Hepatitis B Virus, Duck / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000517:prevention & control*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D020135:Peptide Nucleic Acids / Q000008:administration & dosage; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001704:Biopolymers; D002412:Cations; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D017325:Hepatitis B Vaccines; D020135:Peptide Nucleic Acids; D048271:Chitosan
keywords: DNA vaccine; antigen (Ag); antiviral therapy; catonic polymers; cell penetrating peptides (CPPs); chitosan (CS); duck hepatitis B virus (DHBV); gene delivery; hepatitis B; hepatitis B virus (HBV); peptide nucleic acids (PNAs)