Lipofectamine® 3000, a reagent for nucleic acid delivery, was designed to enhance transfection efficiency in difficult-to-transfect cells while reducing cytotoxicity-associated cell alteration. The reagent was also designed for versatility—it can work with a broad spectrum of cell lines. Also, a single kit can transfect DNA or RNA or accomplish co-transfection. With this new reagent, GeneArt® TALs and CRISPR can target the AAVS1 locus in HepG2 and U2OS cells, which can improve transfection efficiency, mean fluorescence intensity, and genomic cleavage. These advancements in delivery can help simplify downstream workflows, enable easier stem cell manipulation, and enhance site-specific insertion of transgenes into the cellular genome.