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

• Published in: Nano research 2018-12, Vol.11 (12), p.6270-6282
• Main Authors: Li, Min, Fan, Ya-Nan, Chen, Zhi-Yao, Luo, Ying-Li, Wang, Yu-Cai, Lian, Zhe-Xiong, Xu, Cong-Fei, Wang, Jun
• Format: Article
• Language: English
• Subjects: Arthritis; Atomic/Molecular Structure and Spectra; Biomedicine; Biotechnology; Chemistry and Materials Science; Clonal deletion; Condensed Matter Physics; CRISPR; Deoxyribonucleic acid; Diseases; DNA; Effector cells; Gene deletion; Genetic modification; Genome editing; In vivo methods and tests; Inflammatory diseases; Insertion; Intervention; Lymphocyte receptors; Lymphocytes B; Materials Science; Medical treatment; Nanoparticles; Nanotechnology; Polyethylene glycol; Research Article; Rheumatoid arthritis
• ISSN: 1998-0124; 1998-0000
• DOI: 10.1007/s12274-018-2150-5

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 (NP Cas9/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 NP Cas9/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.