MS2 VLP-based delivery of microRNA-146a inhibits autoantibody production in lupus-prone mice
Yang Pan,1,2 Tingting Jia,1,2 Yuan Zhang,1,2 Kuo Zhang,1 Rui Zhang,1 Jinming Li,1 Lunan Wang1
1National Center for Clinical Laboratories, Beijing Hospital of the Ministry of Health, Beijing, People’s Republic of China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
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), Interleukin-1β (Il-1β) and Interleukin-6 (Il-6). 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.
Keywords: systemic lupus erythematosus, anti-dsDNA antibody, autoantibody to nuclear antigen, Toll-like receptor, BXSB mice, gene therapy.
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]
Readers of this article also read:
Enhancing microparticle internalization by nonphagocytic cells through the use of noncovalently conjugated polyethyleneimine
Patiño T, Nogués C, Ibáñez E, Barrios L
Published Date: 8 November 2012
Vardharajula S, Ali SZ, Tiwari PM, Eroğlu E, Vig K, Dennis VA, Singh SR
Published Date: 9 October 2012
Liver cell specific targeting by the preS1 domain of hepatitis B virus surface antigen displayed on protein nanocages
Murata M, Narahara S, Umezaki K, Toita R, Tabata S, Piao JS, Abe K, Kang JH, Ohuchida K, Cui L, Hashizume M
Published Date: 9 August 2012
The scent fingerprint of hepatocarcinoma: in-vitro metastasis prediction with volatile organic compounds (VOCs)
Amal H, Ding L, Liu BB, Tisch U, Xu ZQ, Shi DY, Zhao Y, Chen J, Sun RX, Liu H, Ye SL, Tang ZY, Haick H
Published Date: 30 July 2012
Marusza W, Mlynarczyk G, Olszanski R, Netsvyetayeva I, Obrowski M, Iannitti T, Palmieri B
Published Date: 27 July 2012
Lysine-functionalized nanodiamonds: synthesis, physiochemical characterization, and nucleic acid binding studies
Kaur R, Chitanda JM, Michel D, Maley J, Borondics F, Yang P, Verrall RE, Badea I
Published Date: 19 July 2012
Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α
Manoharan Y, Ji Q, Yamazaki T, Chinnathambi S, Chen S, Ganesan S, Hill JP, Ariga K, Hanagata N
Published Date: 16 July 2012
NC-6301, a polymeric micelle rationally optimized for effective release of docetaxel, is potent but is less toxic than native docetaxel in vivo
Harada M, Iwata C, Saito H, Ishii K, Hayashi T, Yashiro M, Hirakawa K, Miyazono K, Kato Y, Kano MR
Published Date: 31 May 2012
Iancu C, Mocan L
Published Date: 21 October 2011