Therapeutic Potential of Cell Penetrating Peptides (CPPs) and Cationic Polymers for Chronic Hepatitis B

International Journal of Molecular Sciences

Bénຝicte Ndeboko¹  Guy Joseph Lemamy²  Peter. E Nielsen³  Lucyna Cova¹ 

[1] Institut National de la Sante et Recherche Medicale (INSERM) U1052, Cancer Research Center of Lyon (CRCL), Lyon 69003, France;Département de Biologie Cellulaire and Moléculaire-Génétique, Faculté de Médecine, Université des Sciences de la Santé, Libreville 241, Gabon;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;

关键词: hepatitis B;    antiviral therapy;    cell penetrating peptides (CPPs);    chitosan (CS);    catonic polymers;    peptide nucleic acids (PNAs);    hepatitis B virus (HBV);    duck hepatitis B virus (DHBV);    DNA vaccine;    gene delivery;    antigen (Ag);   

DOI  :  10.3390/ijms161226094

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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