The invention provides methods for autocatalytic genome editing based on genomic integration of a construct containing multiple elements. More specifically, the invention provides a method for autocatalytic genome editing or for deleting or neutralizing autocatalytic genome editing based on the CRISPR/Cas9 system, and methods of use thereof, in animals, humans, and plants for eliminating pathogens, targeting suppression of crop pests, strategies to combat virus (e.g., HIV) and other diseases (e.g., cancer) caused by retrovirus, as well as to generate, and reverse, homozygous mutations that are transmitted to nearly all offspring.