| Method | Advantages | Limitations |
| Needle injection Direct needle injection on a specific tissue | Simple Safe | Low efficiency Local inflammation |
| Hydrofection or hydrodynamic injection Intravascular injection of high volumes of a solution containing the nucleic acids | High efficacy in the Liver | Hemodynamic changes |
| Microinjection Direct injection into host cell by microneedles | High efficiency | Cell by cell administration Time-consuming Need of specialist |
| Biolistic injection or gene gun Administration of metal microparticles at high velocity | Simple and fast Reproducibility | Low efficiency Low tissue penetration Cell damage High cost |
| Electroporation Application of electric pulses that open pores on cell membrane | Noninvasive Simple High efficiency Low cost Widely employed | Risk of tissue damage Surgery necessary to target internal organs |
| Sonoporation Application of ultrasounds (combined with microbubbles or nanocarriers) to permeabilize temporally cell membrane | Noninvasive Safe Targeting to specific tissues | Low reproducibility Tissue damage |
| Magnetofection Application of external magnetic fields combined with magnetic particles | Noninvasive Effective in primary cells (difficult to transfect) | Effective only on surface areas Mainly applied in vitro |
| Optofection Application of laser pulses combined with nucleic acid complexes or nanoparticles | Nucleic acids release from endosomes | Tissue damage Inflammation Restricted to single cells or small areas |