Table 1.
Comparison of different in vivo antibody gene delivery platforms
| Synthetic DNA | mRNA | Viral vector | |
|---|---|---|---|
| Starting material | Plasmid DNA | Plasmid DNA | Plasmid DNA |
| Injected material | Plasmid DNA/by EP | mRNA in LNP | AAV, Ad vector |
| In vivo product | mAb, BsMAb | mAb, BsMAb | mAb, BsMAb |
| Transient | Yes | Yes | Yes; however, rare cases may integrate (AAV) |
| Cell compartment | Nucleus | Cytoplasm | Nucleus |
| Integration | None observed in humans | Low probability data early | Possible [14] |
| Anti-vector immunity | No | No | Yes, serotype specific |
| Duration of a single administration | Weeks/months | Days/weeks | Months/years |
| Delivery route | ID, IM | IV, IM/ID | IM, IN, IV, IC, IO, IT |
| Tissue specificity/tropism | Local site of administration | Non-specific | Serotype dependent |
| Vector take | High in animals | High in preclinical | Variable |
| Human safety | Very safe, no SAEs in 1000s of individuals | Ongoing trials, SAEs reported [15] | Safe but potential for integration (AAV) |
| Ease of manufacturing | Yes | Likely yes with caveats | Moderate |
| Cold-chain free | Yes |
Possible (with LNP) No (without LNP) |
No |
AAV adenovirus-associated virus, Ad adenovirus, BsMAb bispecific mAb, EP electroporation, IC intracranial, ID intradermal, IM intramuscular, IN intranasal, IO intraocular (subretinal and intravitreal), IT intrathecal, IV intravenous, LNP lipid nanoparticle, mAb monoclonal antibody, mRNA messenger RNA, SAEs serious adverse events