Compositions and methods concern the sequence modification of an endogenous genomic DNA region. Certain aspects relate to a method for site-specific sequence modification of a target genomic DNA region in cells comprising: contacting the cells with an activating composition transfecting the cells with a transfection composition comprising (a) donor DNA and (b) a DNA digesting agent wherein the donor DNA comprises: (i) a homologous region comprising nucleic acid sequence homologous to the target genomic DNA region and (ii) a sequence modification region and wherein the genomic DNA sequence is modified specifically at the target genomic DNA region.
