Sickle cell disease (SCD) results from a point mutation in the β-globin gene that leads to the production of hemoglobin S. This abnormal form of hemoglobin causes red blood cells to take on a sickle shape, reducing their flexibility and increasing the likelihood of hemolysis and vascular occlusion. The mutation is responsible for the key symptoms of SCD, such as chronic anemia, vaso-occlusive crises and multi-organ complications. A potential cure for SCD involves correcting the β-globin gene mutation through targeted genome editing. In our research, we compared our proprietary HDR-Cas9 fusion (which combines Cas9 with CtIP and dnRNF168) to unmodified Cas9. We used highly efficient gRNAs targeting the HBB locus in K562 cells and identified G10/R-02 as the most effective guide for introducing single base substitutions using a non-symmetric single-stranded repair template. Using the G10/R-02 gRNA, we tested different repair template designs while simulating the SCD mutation. Our results showed that HDR-Cas9 exhibited superior precision in making single base substitutions compared to unmodified Cas9 across all repair templates tested. The most remarkable results were achieved using a double-stranded repair template that included Cas9 target sites for improved nuclear shuttling, which resulted in approximately 2.4 fold of error-free editing. These results validate the efficacy of our HDR-Cas9 fusion and highlight the potential benefits of enhancing HDR factors at the target site to improve precision in genome editing, especially at the single base level.