Targeted delivery of therapeutics is of great interest to reduce toxicity and immunogenicity of the treatment. In particular, the liver is an ideal target for nucleic acid therapeutics due to its large size, regenerative capacity, and the role in producing serum proteins. In this work, N-acetyl-D-galactosamine (GalNAc) ligands clustered into a polymeric architecture were studied for enhanced binding to the asialoglycoprotein receptors (ASGPRs) on hepatocytes. A series of cationic glycopolymers based on this architecture was used to encapsulate plasmids (pDNA) into polymer-pDNA complexes (polyplexes) and deliver them to receptor-specific cells. The GalNAc-derived polyplexes were colloidally stable and showed cell type-specific gene expression in cultured cells. This work demonstrated the versatility of glycopolymers in selective delivery of therapeutics to cells of interest. We sought to further understand the role of such gene-delivery vehicles in genome editing applications using the CRISPR/Cas9 system. Our results show that the gene delivery vehicle can play a role in promoting homology-directed repair over nonhomologous end joining based on its gene delivery properties. The frequency of editing correlates with the fraction of cells expressing Cas9 above a certain threshold and higher expression does not contribute to any gains in editing efficiency. Taken together, these observations suggest that future gene-delivery vehicles aimed for genome editing applications should be designed to deliver only a sufficient amount of DNA but to a large fraction of cells.