Table 1.
Comparison of studies on PCSK9 editing in non-human primates.
| First Author, Journal (Year of Publication) [Reference] |
Wang, Nature Biotechnology (2018/2021) [40,41] |
Musunuru, Nature (2021) [6] |
Rothgangl, Nature Biotechnology (2021) [44] |
|---|---|---|---|
| Non-human primate | Rhesus macaques (Macaca mulatta) |
Cynomolgus macaques (Macaca fascicularis) |
Cynomolgus macaques (Macaca fascicularis) |
| Delivery method | Adeno-associated virus transducing genetic information for the meganuclease | Lipid nanoparticle containing gRNA and base editor mRNA | Lipid nanoparticle containing gRNA and base editor mRNA |
| Genome editing technology | Meganuclease, induction of double strand breaks at specific site, random deletions/insertions after repair | Adenine base editor, specific single-nucleotide exchange | Adenine base editor, specific single-nucleotide exchange |
| Length of follow-up | Up to 3 years | 8 months | 29 days |
| PCSK9 editing * | Up to 46% | 66% | Max. 34%, mean 26% |
| Reduction PCSK9 | Up to 84% | 90% | 32% |
| Reduction LDL-C | Up to 60% | 60% | 14% |
| Off-target effects | Up to 629 detected off-target DNA cleavages | None detected | None detected |
| Immune response | T cell response | None detected | Humoral immune response against base editor |