Cationic Lipids & Ionizable Lipids
The molecular architecture of cationic lipids used as nucleic acid carriers is similar to that of natural lipids, with the major difference being their cationic head group, so cationic lipids have the ability to form aggregate complexes with anionic nucleic acids such as DNA or RNA. Advantages of cationic lipid-mediated transfection include high efficiency, ability to transfect a wide range of cell types, reproducibility, and simplicity.
Ionizable cationic lipids (including DOTMA, DODAP, DLin-KC2-DMA, and D-Lin-MC3-DMA) are pH sensitive and highly effective for in vivo transfection. These ionizable cationic lipids are positively charged at low pH (the ability to complex nucleic acids), but mostly uncharged at the pH of blood (pH 7.4) (slow elimination and good tolerability). The ionizable cationic lipids shape and acid-dissociation constant optimization dramatically improved lipid nanoparticles (LNPs) potency, thereby enabling clinical translation.
- Formula: C44H78N2O4
- Molecular Weight: 699.10
AA3-DLin is a biodegradable ionizable cationic lipid (pKa = 5.8). AA3-DLin is used to combine mRNA with lipid nanoparticles (LNPs) for delivery, thereby achieving endosomal escape and cytoplasmic release. AA3-DLin can be used in research on type 2 diabetes, steroid-resistant asthma, lung cancer, ischemic stroke, breast cancer, melanoma, and COVID-19.
- Formula: C50H93N3O2
- Molecular Weight: 768.29
- Formula: C46H73N5O2
- Molecular Weight: 728.10
- Formula: C61H107N3O6
- Molecular Weight: 978.52
Lipid 331 is an ionizable lipid that can be used for the generation of lipid nanoparticles (LNPs). Lipid 331 is a carrier for both siRNA and mRNA.
- Formula: C47H87N3O2
- Molecular Weight: 726.21
- Formula: C42H77NO2
- Molecular Weight: 628.07
YSK 05 is a pH-sensitive cationic lipid. YSK 05 improves the intracellular trafficking of non-viral vectors. YSK 05-MEND shows significantly good gene silencing activity and hemolytic activity. YSK 05 overcomes the suppression of endosomal escape by PEGylation. YSK 05 effectively enhances siRNA delivery both in vitro and in vivo.
- Formula: C92H160N4O10
- Molecular Weight: 1482.28
OF-Deg-Lin is an ionizable amino lipid used for the generation of Lipid nanoparticles (LNPs).
- Formula: C36H60N2O4S4
- Molecular Weight: 713.13
NT1-O12B, an endogenous chemical and a neurotransmitter-derived lipidoid (NT-lipidoid), is an effective carrier for enhanced brain delivery of several blood-brain barrier (BBB)-impermeable cargos. Doping NT1-O12B into BBB-impermeable lipid nanoparticles (LNPs) gives the LNPs the ability to cross the BBB. NT-lipidoids formulation not only facilitate cargo crossing of the BBB, but also delivery of the cargo into neuronal cells for functional gene silencing or gene recombination.
- Formula: C60H111N3O6
- Molecular Weight: 970.54
244cis, a piperazine-containing ionizable cationic lipid, has been used to generate lipid nanoparticles (LNPs). LNPs containing 244cis and coated with mRNA reporter gene were specifically accumulated in mouse lungs compared with LNPs containing SM-102. Induces a decrease in serum chemokine (C-C motif) ligand 2 (CCL2) levels.
- Formula: C44H81NO2
- Molecular Weight: 656.12
DLin-K-C3-DMA, a cationic lipid, can be used in the synthesis of nucleic acid-lipid particle to delivery of nucleic acid.
- Formula: C42H71NO7
- Molecular Weight: 702.02
LNP Lipid-8 (11-A-M) is an ionizable single-tail multi-head lipid that can be used as a lipid nanoparticle (LNP) to deliver siRNA to T cells without targeting ligands. LNP Lipid-8 is more selective for T cells than other cell types such as hepatocytes. LNP Lipid-8 selectively delivers siRNA/sgRNA to T cells (especially CD8+ T cells) through endogenous lipid transport pathways, and can enter cells and release RNA through endocytosis to achieve gene silencing. LNP Lipid-8 loaded with GFP siRNA (siGFP) significantly led to GFP gene silencing in mouse models. LNP Lipid-8 showed good efficacy and safety in both cells and animals, without obvious liver targeting and toxicity. LNP Lipid-8 can be used for RNA delivery research in the fields of tumor immunotherapy and T cell-mediated autoimmune diseases.
- Formula: C38H76ClN
- Molecular Weight: 582.47
Dioleyldimethylammonium chloride (DODAC) is a positively charged lipid promoter with membrane-disrupting activity, which is often formulated into cationic liposomes with dioleoylphosphatidylethanolamine. Dioleyldimethylammonium chloride is used in gene transfection research; through electrostatic interactions, it effectively promotes the binding of programmable fusion vesicles to cells and induces membrane disruption. Dioleyldimethylammonium chloride is also applied in studies on L1210 leukemia and LS180 human colon cancer.
- Formula: C120H222N6O15
- Molecular Weight: 1989.08
FTT5 is an ionizable lipid that can be used to prepare lipid nanoparticles for efficient delivery of long-chain mRNA in vivo.
- Formula: C50H99NO7
- Molecular Weight: 826.32
- Formula: C65H126N4O6
- Molecular Weight: 1059.72
AA-T3A-C12 is an anisamide ligand-tethered lipidoid (AA-lipidoid). AA-T3A-C12 mediates great RNA delivery and transfection of activated fibroblasts.
- Formula: C93H173N5O20S5.xC2HF3O2
- Molecular Weight: 1841.72 (free base)
5A2-SC8 TFA is an ionizable amino lipid in lipid nanoparticles (LNPs) that shows high delivery potential and low in vivo toxicity, enabling efficient delivery of small RNAs such as siRNA and miRNA into tumor cells. 5A2-SC8 TFA LNPs can confer a unique delivery fate of RNA within the liver, thereby changing the therapeutic outcomes in cancer models.
- Formula: C58H114N2O5
- Molecular Weight: 919.54
Ionizable lipid-1 (compound II-10) is an ionizable lipid (pKa=6.16) that can be used to prepare lipid nanoparticles (LNP) with bilayer structure.
- Formula: C44H82N2O2
- Molecular Weight: 671.13
Lipid 8 is an ionizable amino lipid that can be used to synthesize lipid nanoparticles (LNPs). Lipid 8 is applicable to research in drug delivery.
