The invention provides methods and compositions that remove target genetic material from a subject by delivery of an enzyme that degrades the target genetic material. The methods include delivering a composition of a nucleic acid to a tissue, such as skin, of a subject along with various types of energy to enhance permeability of the tissue and cause the nucleic acid to enter cells of the tissue, wherein the nucleic acid comprises a gene for an enzyme that cuts target genetic material. The nucleic acid may be a plasmid comprising a