The article presents a novel method for efficient intracellular delivery of proteins, particularly genome-editing enzymes, using cationic lipid nucleic acid transfection reagents. The authors demonstrate that proteins fused to negatively supercharged proteins, containing natural anionic domains, or natively binding to anionic nucleic acids can be effectively delivered into cultured human cells and mouse inner ears. This approach significantly improves the efficiency and specificity of genome editing compared to traditional methods such as plasmid DNA transfection and viral delivery. The study shows that cationic lipid-mediated delivery of Cre recombinase, TALE-based transcriptional activators, and Cas9:sgRNA complexes can achieve up to 80% genome modification in cultured cells and 90% Cre-mediated recombination and 20% Cas9-mediated genome modification in mouse inner ear hair cells. The method also exhibits reduced off-target effects, making it a promising tool for therapeutic applications.The article presents a novel method for efficient intracellular delivery of proteins, particularly genome-editing enzymes, using cationic lipid nucleic acid transfection reagents. The authors demonstrate that proteins fused to negatively supercharged proteins, containing natural anionic domains, or natively binding to anionic nucleic acids can be effectively delivered into cultured human cells and mouse inner ears. This approach significantly improves the efficiency and specificity of genome editing compared to traditional methods such as plasmid DNA transfection and viral delivery. The study shows that cationic lipid-mediated delivery of Cre recombinase, TALE-based transcriptional activators, and Cas9:sgRNA complexes can achieve up to 80% genome modification in cultured cells and 90% Cre-mediated recombination and 20% Cas9-mediated genome modification in mouse inner ear hair cells. The method also exhibits reduced off-target effects, making it a promising tool for therapeutic applications.