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Efficient delivery of HBV NLS siRNAs into HepG2.2.15 cells for HBV inhibition through novel recombinant preS1tP proteins

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Hepatitis B virus (HBV) infection and related liver complications remain severe public health problems worldwide. Previous investigations have shown that small interfering (si)RNAs can offer an effective strategy for the treatment of chronic hepatitis B. The present study aimed to develop a novel siRNAdelivering system of therapeutic HBV nuclear localization sequence (NLS) siRNAs using the recombinant preS1truncated protamine (tP) proteins. The preS1 region of the LHB was used in place of scFv to construct the recombinant preS1tP proteins, which were applied to deliver siRNAs targeting the HBV NLS to inhibit HBV replication and infection in HepG2.2.15 cells overexpressing sodium taurocholate cotransporting polypeptide (NTCP). The results revealed that HepG2.2.15 cells with stable NTCP expression (HepG2.2.15NTCP cells) transfected with the recombinant lentivirus showed increased expression of NTCP genes. The HBV NLS siRNAs significantly suppressed HBV mRNA content and levels of HBsAg and HBeAg in the HepG2.2.15NTCP cells. Recombinant preS1tP proteins tagged with His and glutathione Stransferase were found to enter into HepG2.2.15NTCP cells and bind with DNA. The HBV NLS siRNAs were delivered into HepG2.2.15NTCP cells by recombinant preS1tP proteins, which resulted in decreased expression of HBV mRNA, HBsAg and HBeAg, HBV DNA and covalently closed circular DNA in the HepG2.2.15NTCP cells. Therefore, the recombinant preS1tP proteins successfully delivered NLS siRNAs into HepG2.2.15 cells and repressed HBV infection and replication.
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Document Type: Research Article

Affiliations: 1: Department of Infectious Diseases, Zhengzhou University People's Hospital, Henan University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China 2: Tongji Medical College of Huazhong University of Science and Technology Affiliated Hospital of Traditional Chinese and Western Medicine, Wuhan, Hubei 430030, P.R. China

Publication date: January 1, 2018

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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