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Optimized nanoparticle-mediated delivery of CRISPR-Cas9 system for B cell intervention

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Abstract

B cells exert multiple effector functions, and dysfunctions of B cells often lead to initiation and progression of diseases, including autoimmune and inflammatory diseases. Therefore, B cell intervention may be an effective strategy to treat diseases involving B cells. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing system has been widely used for DNA deletion, insertion, and replacement. Nanocarriers have been developed as relatively mature systems and may be applied to deliver the CRISPR-Cas9 system to B cells in vivo. In this study, we created a library of nanoparticles (NPs) with different polyethylene glycol densities and zeta potentials and screened an optimal NP for in vivo B cell targeting. The selected NP could deliver the CRISPR-Cas9 system to B cells and induce Cas9 expression inside the cell environment. Injection of the NP encapsulated with Cas9/gB220 (NPCas9/gB220) into mice could disrupt B220 expression in B cells, suggestive of its applications to intervene the expression of the target molecule in B cells. Moreover, the treatment with NPCas9/gBAFFR could decrease the number of B cells and exert therapeutic effect in rheumatoid arthritis, as B-cell activating factor receptor (BAFFR) is vital for the survival and functions of B cells. In conclusion, we developed a carrier for the delivery of the CRISPR-Cas9 gene editing system for B cell intervention that could be used for the treatment of diseases related to B cell dysfunctions.

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Acknowledgements

This work was supported by the National Key R&D Program of China (No. 2017YFA0205600), the National Basic Research Program of China (No. 2015CB932100), the National Natural Science Foundation of China (Nos. 551390482 and 51633008), the China Postdoctoral Science Foundation (Nos. 2016M590582 and 2018M630953), and the Fundamental Research Funds for the Central Universities.

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  1. Min Li and Ya-Nan Fan contributed equally to this work.

Authors and Affiliations

  1. School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China

    Min Li, Ya-Nan Fan, Zhi-Yao Chen, Ying-Li Luo & Yu-Cai Wang

  2. Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, 510006, China

    Zhe-Xiong Lian, Cong-Fei Xu & Jun Wang

  3. School of Biomedical Science and Engineering, South China University of Technology, Guangzhou, 510006, China

    Zhe-Xiong Lian, Cong-Fei Xu & Jun Wang

  4. National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, China

    Jun Wang

  5. Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou, 510006, China

    Jun Wang

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  1. Min Li
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Correspondence to Cong-Fei Xu or Jun Wang.

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Li, M., Fan, YN., Chen, ZY. et al. Optimized nanoparticle-mediated delivery of CRISPR-Cas9 system for B cell intervention. Nano Res. 11, 6270–6282 (2018). https://doi.org/10.1007/s12274-018-2150-5

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