Risks of genome editing
| Toxicity . | Potential risks . |
|---|---|
| Genotoxicity | (On-target) Local mutations at target locus: insertions/deletions, base substitutions; end capture of donor, 1 sided or nonhomologous recombination, and unintended gross chromosomal rearrangements; (off-target) mutations at sites other than target locus, including gross chromosomal rearrangements |
| Potential consequences: local gene inactivation, dysregulation, trans-activation; deletions, inversions, translocations; transformation, cell cycle disruptions, apoptosis | |
| Nuclease related | Off-target endonuclease activity |
| Persistent endonuclease activity (off-target mutations and/or activation of the DNA damage response) | |
| Immunogenicity | |
| Vector related (nucleic acids, nucleoproteins, nanoparticles, viral vectors) | Random integration of donor vector (illegitimate recombination at a spontaneous or induced DSB) leading to local gene inactivation, dysregulation, trans-activation |
| Random integration of nuclease expression vector (illegitimate recombination at a spontaneous or induced DSB) leading to persistent nuclease expression | |
| Delivery related (transfection, microinjection, electroporation, viral vector) | Acute cytotoxicity |
| Induction of inflammatory responses to vector components | |
| Delivery device related (needles, catheters, transplants, stereotactic, electroporation in vivo) | Tissue injury/inflammation |
| Infection | |
| Mechanical mishaps | |
| Ex vivo cell processing related | Cell survival |
| Microbial contamination | |
| Loss of stem cell activity and/or engraftment activity; impaired differentiation/function; inherent genome instability during culture |
| Toxicity . | Potential risks . |
|---|---|
| Genotoxicity | (On-target) Local mutations at target locus: insertions/deletions, base substitutions; end capture of donor, 1 sided or nonhomologous recombination, and unintended gross chromosomal rearrangements; (off-target) mutations at sites other than target locus, including gross chromosomal rearrangements |
| Potential consequences: local gene inactivation, dysregulation, trans-activation; deletions, inversions, translocations; transformation, cell cycle disruptions, apoptosis | |
| Nuclease related | Off-target endonuclease activity |
| Persistent endonuclease activity (off-target mutations and/or activation of the DNA damage response) | |
| Immunogenicity | |
| Vector related (nucleic acids, nucleoproteins, nanoparticles, viral vectors) | Random integration of donor vector (illegitimate recombination at a spontaneous or induced DSB) leading to local gene inactivation, dysregulation, trans-activation |
| Random integration of nuclease expression vector (illegitimate recombination at a spontaneous or induced DSB) leading to persistent nuclease expression | |
| Delivery related (transfection, microinjection, electroporation, viral vector) | Acute cytotoxicity |
| Induction of inflammatory responses to vector components | |
| Delivery device related (needles, catheters, transplants, stereotactic, electroporation in vivo) | Tissue injury/inflammation |
| Infection | |
| Mechanical mishaps | |
| Ex vivo cell processing related | Cell survival |
| Microbial contamination | |
| Loss of stem cell activity and/or engraftment activity; impaired differentiation/function; inherent genome instability during culture |