Gene targeting versus random insertion

Random insertion can take place anywhere in the genomic DNA, and maintains the HSV-TK element, which is toxic and kills the cells into which it has integrated in the presence of gancyclovir.

Gene targeting takes place at one of two alleles of the homologous chromosomal site. The double crossover event eliminates the HSV-TK element, rendering the cells resistant to gancyclovir.

from Cappechi, redrawn SPW