Development of an antisense RNA delivery system using conjugates of the MS2 bacteriophage capsids and HIV-1 TAT cell penetrating peptide

Wei, Bojun; Wei, Yuxiang; Zhang, Kuo; Wang, Jing; Xu, Run; Zhan, Sien; Lin, Guigao; Wang, Wei; Liu, Min; Wang, Lunan; Zhang, Rui; Li, Jinming

doi:10.1016/j.biopha.2008.07.086

Cited by 74 publications

(57 citation statements)

References 31 publications

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“…Virus based delivery agents are generally considered to be highly efficient (Liu and Berkhout, 2011;Usme Ciro et al, 2013;Wei et al, 2009;Chou et al, 2010;Choi et al, 2013;Rao et al, 2013). The ability of viral capsids to assemble into nanoparticles in the presence of DNA oligonucleotides Tellinghuisen et al, 1999), yeast tRNA (Tellinghuisen et al, 1999), or siRNA (Choi et al, 2013) is known.…”

Section: Discussionmentioning

confidence: 99%

siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells

Kumar

Reddy

Rajmane

et al. 2015

Journal of Biotechnology

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Section: Discussionmentioning

confidence: 99%

siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells

Kumar

Reddy

Rajmane

et al. 2015

Journal of Biotechnology

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“…The 20% denaturing PAGE showed that the molecular weight of MS2-miR146a and MS2-miRNC VLPs was approximately 14 kDa, while the Tat47-57 conjugated VLPs exhibited retarded mobility ( Figure 1C). 19 The denaturing PAGE also indicated that about 24% and 26% of total MS2-miR146a VLPs and MS2-miRNC VLPs, respectively, were conjugated to the Tat peptide.…”

Section: Expression Of the Ms2 Vlp-based Mir-146a Delivery Vehiclementioning

confidence: 93%

MS2 VLP-based delivery of microRNA-146a inhibits autoantibody production in lupus-prone mice

Pan¹,

Jia²,

Zhang³

et al. 2012

IJN

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Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of pathogenic autoantibodies. Recent studies suggest that microRNAs (miRNAs) play an essential role in immunoregulation and may be involved in the pathogenesis of SLE. Therefore, it was of interest to investigate the potential therapeutic application of miRNAs in SLE, a concept that has not been thoroughly investigated thus far. Virus-like particles (VLPs) are a type of recombinant nanoparticle enveloped by certain proteins derived from the outer coat of a virus. Herein, we describe a novel miRNA-delivery approach via bacteriophage MS2 VLPs and investigate the therapeutic effects of miR-146a, a well-studied and SLE-related miRNA, in BXSB lupus-prone mice. Methods: VLPs containing miR-146a, and the control VLPs, were prepared using an Escherichia coli expression system and then administered to lupus-prone mice over a 12-day period. We performed an enzyme-linked immunosorbent assay to evaluate the anti-dsDNA antibody, autoantibody to nuclear antigen (ANA), total IgG and total IgM levels in serum. The expression of miR-146a was analyzed by qRT-PCR. SLE-related cytokines as well as some toll-like receptor signaling pathway molecules were also measured. Results: Treatment with MS2-miR146a VLP showed profound effects on lupus-prone BXSB mice, including an increased level of mature miR-146a, which led to a significant reduction in the expression of autoantibodies and total IgG. Remarkably, these mice also exhibited reduced levels of proinflammatorycytokines, including IFN-Interferon-α (IFN-α), and . Moreover, we showed that the toll-like receptor pathway was involved in this regulation. Conclusion: Restoring the loss of miR-146a was effective in eliminating the production of autoantibodies and ameliorating SLE progression in lupus-prone mice. Thus, the induction of dysregulated miRNAs by an MS2 VLP-based delivery system may lead to novel therapies.

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“…By packing the antisense RNA, directed at the 5′UTR and IRES sequences of HCV, in self-assembling MS2 bacteriophage capsids, the oligonucleotides were protected against degradation in vitro and in vivo. However, the high level of antisense oligonucleotides needed to inhibit HCV replication was toxic to the cells [ 205 ]. A more promising approach may use miravirsen, a 15-nt oligonucleotide that is complementary to miR-122 and thus interferes with HCV replication.…”

Section: Mirna Blocking With Antisense Technologymentioning

confidence: 98%

Gene Therapies for Hepatitis C Virus

Verstegen

Pan

Laan

2015

Advances in Experimental Medicine and Biology

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Hepatitis C virus (HCV) is a leading cause of chronic hepatitis and infects approximately three to four million people per year, about 170 million infected people in total, making it one of the major global health problems. In a minority of cases HCV is cleared spontaneously, but in most of the infected individuals infection progresses to a chronic state associated with high risk to develop liver cirrhosis, hepatocellular cancer, or liver failure. The treatment of HCV infection has evolved over the years. Interferon (IFN)-α in combination with ribavirin has been used for decades as standard therapy. More recently, a new standard-of-care treatment has been approved based on a triple combination with either HCV protease inhibitor telaprevir or boceprevir. In addition, various options for all-oral, IFN-free regimens are currently being evaluated. Despite substantial improvement of sustained virological response rates, some intrinsic limitations of these new direct-acting antivirals, including serious side effects, the risk of resistance development and high cost, urge the development of alternative or additional therapeutic strategies. Gene therapy represents a feasible alternative treatment. Small RNA technology, including RNA interference (RNAi) techniques and antisense approaches, is one of the potentially promising ways to investigate viral and host cell factors that are involved in HCV infection and replication. With this, newly developed gene therapy regimens will be provided to treat HCV. In this chapter, a comprehensive overview guides you through the current developments and applications of RNAi and microRNA-based gene therapy strategies in HCV treatment.

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Development of an antisense RNA delivery system using conjugates of the MS2 bacteriophage capsids and HIV-1 TAT cell penetrating peptide

Cited by 74 publications

References 31 publications

siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells

siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells

MS2 VLP-based delivery of microRNA-146a inhibits autoantibody production in lupus-prone mice

Gene Therapies for Hepatitis C Virus

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