It depends on the experimental purpose and host cell line. When compared to double-stranded DNA donors, ssDNAs demonstrated significantly improved editing efficiency and specificity, as well as reduced off-target integration, especially in editing primary cells, stem cells, and developing transgenic animal model.
| Plasmid DNA | dsDNA | ssDNA | |
| HDR efficiency | Medium | High | Comparable to dsDNA |
| Off-target rate | Medium | High | Low |
| Cost | Lower | Medium | High |
| Toxicity | High | High | Low |