For over twenty years, the Kmiec laboratory has studied the reaction mechanics, biochemistry and molecular genetics of gene editing in human cells. During the late 90s, this laboratory began a long-term investigation centered on understanding the mechanism and regulation of gene editing using single-stranded DNA oligonucleotides (ODNs). The lab was a pioneering force in developing the use of these specialized ODNs for the treatment of inherited disorders. Building largely on early genetic studies in lower eukaryotes, we were able to define a reaction protocol that can achieve a sustainable level of correction of genetic mutations in human cells. Development of clinical applications for viable cell environments is underway with a particular focus on utilizing nanofiber scaffolds as templates for the expansion of genetically modified cells. These nanofiber scaffolds are constructed from natural biodegradable composite fibers, such as chitosan/PCL, created by electrospinning in both aligned and random configurations. Since the nanofiber constructs are biodegradable, the 3D patchwork is slowly dissolved as the modified or gene corrected cells effectively implanted or simply transported in the target tissue or blood system. The laboratory is also investigating related reaction barriers including a reduced growth potential and the frequency at which gene editing activity takes place. The ultimate goal of all of this translational research is to develop a feasible protocol for the delivery of genetically modified cells into human tissues using biodegradable nanofiber patches. Finally, the laboratory is now centered on the use of TALENs in a combinational approach with the ssODNs for gene editing. This combination will enhance frequency and enable a robust clinical application for diseases such as sickle cell disease. The Kmiec laboratory has been supported by the National Institute of Health R01 (R21) grants continuously since 1996.