mRNA gene delivery studies in hemophilia
| Study . | Lipid delivery . | Target cell . | Recipient . | Outcome . |
|---|---|---|---|---|
| F9 mRNA43 Padua-9 mRNA Ramaswamy, 2017 | LUNAR lipid nanoparticle | Hepatocyte with luciferase reporter | IV injection in mice with HB | Peak FIX 130% with Padua IX and peak FIX 20% with FIX Levels: 4-9 d vs 1-3 d No inhibitor formation No LFT abnormalities |
| BDD-F8 mRNA44 Russick, 2020 | Lipid nanoparticle | HEK293 cells with luciferase reporter | IV injection in mice with HA | Peak FVIII, 0.36 IU/mL at 24 h FVIII, 0.06-0.11 IU/mL at 72 h Reduced blood loss in tail clip Inhibitor with repeat dosing |
| BDD-F8 mRNA45 Chen, 2020 | Lipid nanoparticle | Hepatocyte with luciferase reporter | IV injection in mice with HA and NSG mice with HA | FVIII activity 5-7 days and APTT and ROTEM corrected Inhibitors formed in mice with HA, but not mice with NSG HA |
| F8 mRNA46 Truong, 2022 | Nanoparticle, transposon nanoparticle | Hepatocyte | PiggyBac GT in neonatal wild-type mice; mice with CD4-HA | FVIII:Ag expressed >50% and sustained 5 months in wild-type mice FVIII activity 30%-150% level and sustained 6 months in mice with HA |
| Study . | Lipid delivery . | Target cell . | Recipient . | Outcome . |
|---|---|---|---|---|
| F9 mRNA43 Padua-9 mRNA Ramaswamy, 2017 | LUNAR lipid nanoparticle | Hepatocyte with luciferase reporter | IV injection in mice with HB | Peak FIX 130% with Padua IX and peak FIX 20% with FIX Levels: 4-9 d vs 1-3 d No inhibitor formation No LFT abnormalities |
| BDD-F8 mRNA44 Russick, 2020 | Lipid nanoparticle | HEK293 cells with luciferase reporter | IV injection in mice with HA | Peak FVIII, 0.36 IU/mL at 24 h FVIII, 0.06-0.11 IU/mL at 72 h Reduced blood loss in tail clip Inhibitor with repeat dosing |
| BDD-F8 mRNA45 Chen, 2020 | Lipid nanoparticle | Hepatocyte with luciferase reporter | IV injection in mice with HA and NSG mice with HA | FVIII activity 5-7 days and APTT and ROTEM corrected Inhibitors formed in mice with HA, but not mice with NSG HA |
| F8 mRNA46 Truong, 2022 | Nanoparticle, transposon nanoparticle | Hepatocyte | PiggyBac GT in neonatal wild-type mice; mice with CD4-HA | FVIII:Ag expressed >50% and sustained 5 months in wild-type mice FVIII activity 30%-150% level and sustained 6 months in mice with HA |
CD117, stem cell factor receptor; Cre recombinase, conditional control of gene expression; FVIII:Ag, factor VIII antigen; HSC, hematopoietic stem cells; LFTs, liver function tests; ROTEM, rotational thromboelastometry.