DNA mutations either inherited or acquired during the lifecycle of the cell can affect multiple metabolic pathways. DNA damaging agents accelerate the rate of mutation and in some cases are responsible for the development of serious disease states. While a number of potential therapies are being developed to treat such disorders, the more direct approach is one in which the mutated base is corrected at its chromosomal location. Reversing such mutations would have a serious impact on the disease and likely lead to a permanent correction of some inherited diseases. We have been using end-modified single-stranded DNA oligonucleotides to correct genetic defects in cells by activating the inherent DNA repair pathways and directing their activities to specific mutated sites in the chromosome. By partially elucidating the mechanism of 'gene repair', we have now identified factors that enhance or suppress the frequency of the repair reaction. The regulation of this process is at the heart of its successful application for treating genetic disorders. Proteins such as Rad51 and Rad54 which have been found to control gene repair, are being used therapeutically to increase the frequency and the precision of the repair. We will discuss the use of DNA-associated proteins to promote gene repair and outline the steps we have taken to engineer these enzymes to work even more efficiently.