Abstract
Peptide Nucleic Acid (PNAs) and small noncoding RNAs including small interfering RNAs (siRNAs) represent a new class of oligonucleotides considered as an alternative therapeutic strategy in the chronic hepatitis B treatment. Indeed, chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide, despite the availability of an effective prophylactic vaccine. Current therapeutic approaches approved for chronic HBV treatment are pegylated-interferon alpha (IFN)-α and nucleos(t)ide analogues (NAs). Both therapies do not completely eradicate viral infection and promote severe side effects. In this context, the development of new effective treatments is imperative. This review focuses on antiviral activity of both PNAs and siRNAs targeting hepatitis B virus. Thus, we briefly present our results on the ability of PNAs to decrease hepadnaviral replication in duck hepatitis B virus (DHBV) model. Interestingly, other oligonucleotides as siRNAs could significantly inhibit HBV antigen expression in transient replicative cell culture. Because the application of these oligonucleotides as new antiviral drugs has been hampered by their poor intracellular bioavailability, we also discuss the benefits of their coupling to different molecules such as the cell penetrating peptides (CPPs), which were used as vehicles to deliver therapeutic agents into the cells.
Highlights
Hepatitis B virus (HBV) infection remains a significant public health problem, despite the availability of an effective prophylactic vaccine
Because current drugs approved for chronic hepatitis B treatment only target viral polymerase and show a virostatic effect since rebound of hepatitis B virus (HBV) replication is common after treatment cessation [31], we have evaluated the therapeutic potential of Peptide Nucleic Acids (PNAs) as an alternative antiviral approach
In primary duck hepatocytes (PDH) cultures infected by duck hepatitis B virus (DHBV), we evaluated antiviral effect of anti-ε PNA coupled to polyArginine ((Arg)7) or to nuclear localization signal (NLS) cell penetrating peptides (CPPs)
Summary
Hepatitis B virus (HBV) infection remains a significant public health problem, despite the availability of an effective prophylactic vaccine. Alternative treatment option for patients chronically infected with HBV need to be urgently developed [5,6] In this regard, a new class of oligonucleotides such as Peptide Nucleic Acid (PNA) and small noncoding RNAs (siRNAs) represent an alternative therapeutic strategy in the chronic hepatitis B treatment. PNAs are stable into the cells because they are able to resist to degradation by nucleases and proteases [8] These characteristics make PNAs molecules promising candidates for clinical applications in therapeutic approach of HBV chronic infection. A novel CPP, termed X-pep, from X-protein of HBV has been identified [22] Taken together, these CPPs can cross cell membrane and efficiently deliver various cargoes as PNAs and siRNAs into the cell. Antiviral activity of CPPs used as vehicles will be documented in this review
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