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β-Lactamase Tools for Establishing Cell Internalization and Cytosolic Delivery of Cell Penetrating Peptides
Open AccessArticle

Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway

1
Institut National de la Sante et Recherche Medicale (INSERM) U1052, Cancer Research Center of Lyon (CRCL), 69003 Lyon, France
2
Département de Biologie Cellulaire and Moléculaire-Génétique, Faculté de Médecine, Université des Sciences de la Santé, Libreville 241, Gabon
*
Author to whom correspondence should be addressed.
Biomolecules 2018, 8(3), 55; https://doi.org/10.3390/biom8030055
Received: 14 June 2018 / Revised: 10 July 2018 / Accepted: 11 July 2018 / Published: 16 July 2018
(This article belongs to the Special Issue Cell Penetrating Peptides)
Alternative therapeutic approaches against chronic hepatitis B virus (HBV) infection need to be urgently developed because current therapies are only virostatic. In this context, cell penetration peptides (CPPs) and their Peptide Nucleic Acids (PNAs) cargoes appear as a promising novel class of biologically active compounds. In this review we summarize different in vitro and in vivo studies, exploring the potential of CPPs as vehicles for intracellular delivery of PNAs targeting hepadnaviral replication. Thus, studies conducted in the duck HBV (DHBV) infection model showed that conjugation of (D-Arg)8 CPP to PNA targeting viral epsilon (ε) were able to efficiently inhibit viral replication in vivo following intravenous administration to ducklings. Unexpectedly, some CPPs, (D-Arg)8 and Decanoyl-(D-Arg)8, alone displayed potent antiviral effect, altering late stages of DHBV and HBV morphogenesis. Such antiviral effects of CPPs may affect the sequence-specificity of CPP-PNA conjugates. By contrast, PNA conjugated to (D-Lys)4 inhibited hepadnaviral replication without compromising sequence specificity. Interestingly, Lactose-modified CPP mediated the delivery of anti-HBV PNA to human hepatoma cells HepaRG, thus improving its antiviral activity. In light of these promising data, we believe that future studies will open new perspectives for translation of CPPs and CPP-PNA based technology to therapy of chronic hepatitis B. View Full-Text
Keywords: cell penetrating peptides (CPPs); peptide nucleic acids (PNAs); drug delivery; virus; hepatitis B virus (HBV); duck hepatitis B virus (DHBV); antiviral therapy cell penetrating peptides (CPPs); peptide nucleic acids (PNAs); drug delivery; virus; hepatitis B virus (HBV); duck hepatitis B virus (DHBV); antiviral therapy
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Ndeboko, B.; Hantz, O.; Lemamy, G.J.; Cova, L. Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway. Biomolecules 2018, 8, 55.

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