Table 3.
Selected LNP-based nucleic acid therapeutics in preclinical development. LNPs can deliver siRNA, mRNA, DNA, or gene editing complexes, providing opportunities to treat hepatic diseases by silencing pathogenic genes, expressing therapeutic proteins, or correcting genetic defects.
| Payload | Gene target/product | LNP composition | Cellular target / indication | Administration route | Model | Reference |
|---|---|---|---|---|---|---|
| Gene silencing | ||||||
| siRNA | FVII | DMAP-BLP / DSPC / cholesterol / PEG-DMG (50:10:(39.75 – x):(0.25+x)) | Hepatocytes / Screening | Subcutaneous | C57Bl/6 mice | [147] |
| siRNA | FVII | Ionizable cationic lipid / DSPC / cholesterol / PEG-DMG 40:10:40:10 |
Hepatocytes / Screening | Intravenous | C57BL/6 mice | [31] |
| siRNA | TTR | DLin-MC3-DMA / DSPC / cholesterol / PEG-DMG 50:10:38.5:1.5 |
Hepatocytes / ATTRv amyloidosis | Intravenous | Cynomolgus monkeys | [31] |
| siRNA | ApoB | DLinDMA / DSPC / cholesterol / PEG-C-DMA 40:10:48:2 |
Hepatocytes / Hypercholesterolemia | Intravenous | Cynomolgus monkeys | [133] |
| Gene expression | ||||||
| mRNA | anti-HIV-1 antibody VRC01 | Ionizable cationic lipid / PC / cholesterol / PEG-lipid (50:10:38.5:1.5) | Hepatocytes / Passive immunotherapy against HIV-1 | Intravenous | BALB/C mice | [201] |
| mRNA | Luciferase / Cre-recombinase | DOTMA/DOPE DOTMA/Chol |
Screening | Retro-orbital | NMRI mice / Reporter mice | [209] |
| pDNA | Luciferase | Cationic lipid/Chol-GALA/Malto-PEG6-C11 30:40:30 |
Screening | Intravenous | ICR mice | [174] |
| Gene editing | ||||||
| sgRNA mRNA |
TTR Cas9 |
LP01 / DSPC / cholesterol / PEG-DMG 45:9:44:2 |
Hepatocytes / ATTRv amyloidosis | CD-1 mice Sprague Dawley rats |
[206] | |
| sgRNA mRNA |
PCSK9 Cas9 |
BAMEAO16B / cholesterol / DOPE / DSPE-PEG2000 16:8:4:1 |
Hepatocytes / Hypercholesterolemia | Intravenous | C57BL/6 | [210] |