用于穿透治疗乙型肝炎病毒的寡核苷酸的细胞穿透肽

StephenW

Cell Penetrating Peptides Used in Delivery of Therapeutic Oligonucleotides Targeting Hepatitis B Virus
Bénédicte Ndeboko  1 , Serge Thierry Omouessi  2 , Brice Ongali  1 , Augustin Mouinga-Ondémé  3
Affiliations

    PMID: 33371278 DOI: 10.3390/ph13120483

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.

Keywords: Cell Penetrating Peptides (CPPs); Peptide Nucleic Acids (PNAs); antiviral therapy; drug delivery; duck hepatitis B virus (DHBV); hepatitis B virus (HBV); small interfering RNAs (siRNAs).

StephenW

用于穿透治疗乙型肝炎病毒的寡核苷酸的细胞穿透肽
BénédicteNdeboko 1，Serge Thierry Omouessi 2，Brice Ongali 1，AugustinMouinga-Ondémé3
隶属关系

    PMID：33371278 DOI：10.3390 / ph13120483

抽象

肽核酸（PNA）和小的非编码RNA（包括小干扰RNA（siRNA））代表了一类新的寡核苷酸，被视为慢性乙型肝炎治疗的替代治疗策略。确实，尽管有有效的预防性疫苗，慢性乙型肝炎病毒（HBV）感染仍然是世界范围内的主要公共卫生问题。批准用于慢性HBV治疗的当前治疗方法是聚乙二醇化干扰素α（IFN）-α和nucleot（t）ide类似物（NAs）。两种疗法都不能完全根除病毒感染并促进严重的副作用。在这种情况下，必须开发新的有效疗法。这篇综述主要针对针对乙型肝炎病毒的PNA和siRNA的抗病毒活性。因此，我们简要介绍了有关PNA降低鸭乙型肝炎病毒（DHBV）模型中肝炎病毒复制能力的结果。有趣的是，其他寡核苷酸如siRNA可以在瞬时复制性细胞培养中显着抑制HBV抗原的表达。由于这些寡核苷酸作为新的抗病毒药物的应用已因其不良的细胞内生物利用度而受到阻碍，因此，我们还讨论了它们与不同分子（例如细胞穿透肽（CPPs））偶联的好处，这些分子被用作将治疗剂递送到体内的载体细胞。

关键词：细胞穿透肽（CPPs）；肽核酸（PNAs）；抗病毒治疗；药物输送；鸭乙型肝炎病毒（DHBV）;乙型肝炎病毒（HBV）；小干扰RNA（siRNA）。

StephenW

https://www.mdpi.com/1424-8247/13/12/483/pdf