Optimized Cationic Lipid-Assisted Nanoparticles For Nucleic Acid Drug Delivery To B Cells

B cells exert multiple effector functions and dysfunctions of B cells,which often lead to disease initiation and progression,including autoimmune diseases.Therefore,B cell intervention may be an effective way to treat diseases with B cell involvement.Although small molecule inhibitors and antibodies have revealed remarkable merits in modulating B cells functions and favorable outcomes of autoimmune disease treatments,each has its significant drawbacks and it is urgently needed to develop novel strategies and approaches.With its powerful ability to especially suppress the expression of target genes,RNA interference(RNAi)brings about a new category of treatments for various diseases.In addition,newly developed CRISPR-Cas9 genome-editing systems can intervene in the expression of specific molecules,irrespective of the positioning of the protein,and can have therapeutic effects on diseases induced by genetic change.Nano-carriers have developed into a relatively mature system and may be applied to deliver the siRNA or CRISPR-Cas9 system to B cells in vivo.In this study,we created a library of Cationic Lipid-Assisted Nanoparticles(CLANs)with different PEG densities and zeta potentials and screened an optimal nanoparticle for in vivo B cell targeting.The nanoparticle could deliver the CRISPR-Cas9 system to B cell and help Cas9 expression in the B cell.Injection of the nanoparticle encapsulating siBAFF-R into mice can down-regulate BAFF-R level in B cells,suggesting that we could intervene in the expression of target molecule of B cell.In conclusion,we developed a method of delivering the nucleic acid drugs for B cell intervention by the optimized nanoparticle,and this system can be applied in the treatment of B cell-involved diseases.