Background: CRISPR-Cas9 system is one of the most robust platforms for genome editing and expected as treatment techniques for genetic disorders.  In recent years, to introduce the CRISPR-Cas9 system into the cell, preassembled Cas9/sgRNA complex (Cas9 ribonucleoprotein: Cas9 RNP) has been used because of its higher genome-editing activity than the other genome-editing molecules.  However, Cas9 RNP generally shows low-cell membrane permeability.  Therefore, an efficient intracellular delivery of Cas9 RNP is strongly required.  Meanwhile, we have been reported that dendrimer/glucronylglucosyl-b-cyclodextrin conjugate (GUG-b-CDE) has high gene and nucleic acid transfer activities both in vitro and in vivo.  Objective: Based on these backgrounds, in the present study, we prepared the Cas9 RNP complex with GUG-b-CDE (generation 3: G3), and evaluated the genome-editing activity.  In this study, the neuron and brain were targeted, because induction of genome editing in the neuron and brain was challenging.  Materials and Methods: GUG-b-CDE (G3)/Cas9 RNP complex was prepared by mixing GUG-b-CDE (G3) and Cas9 RNP.  The cellular uptake of the complex in SH-SY5Y cells, a human neuroblastoma cell line, was assayed by a confocal laser microscopy.  The genome-editing activity in the mouse brain was assayed by TIDE analysis after single intraventricular administration of GUG-b-CDE (G3)/Cas9 RNP complex.  Results: GUG-b-CDE (G3)/Cas9 RNP complex exhibited high cellular uptake and genome-editing activity in SH-SY5Y cells, compared to Cas9 RNP alone.  In addition, single intraventricular administration of the complex showed higher genome-editing activity than that of Cas9 RNP alone both around the injection site and in the whole brain.  Moreover, the complex negligibly changed the levels of inflammatory cytokine and microglia marker around the injection site.  Conclusion: GUG-b-CDE (G3) has the potential as a Cas9 RNP carrier possessing the efficient transfer activity in the neuron and brain and high safety after an intraventricular administration.