Ionizable Lipids Overview
Ionizable lipids are lipid molecules that stay neutral at normal physiological pH but gain a positive charge in acidic environments, typically through protonation. For instance, ALC-0315 contains an amine group that becomes protonated at lower pH levels. These lipids are essential in ionizable lipid nanoparticles (LNPs), which are widely used for the systemic delivery of RNA therapeutics. LNPs also include other components like helper lipids, cholesterol, PEG lipids, and more.
Examples of Ionizable Lipids
Common examples of ionizable lipids include ALC-0315, C12-200, cKK-E12, and DLin-MC3-DMA. These lipids become positively charged in acidic conditions, making them valuable for LNP formulations used in RNA delivery and other therapeutic applications.
Advantages
Ionizable lipids offer significant benefits for in vivo mRNA delivery. Their pH-responsive properties reduce interactions with negatively charged blood cell membranes, boosting the biocompatibility of lipid nanoparticles. In the acidic environment of endosomes, ionizable lipids become protonated, gaining a positive charge. This change helps destabilize the membrane, aiding the nanoparticles’ escape from the endosomes. Overall, these lipids enhance endosomal escape and reduce the toxicity associated with lipid nanoparticles during mRNA delivery.
Applications
- mRNA Vaccine Delivery: Ionizable lipids encapsulate and protect mRNA in lipid nanoparticles (LNPs). They promote efficient delivery into cells, making them essential for mRNA vaccines.
- Gene Therapy: These lipids deliver therapeutic genes across cell membranes, improving gene transfer in gene therapy applications.
- Drug Delivery: They increase the solubility and bioavailability of poorly soluble drugs in lipid-based delivery systems.
- siRNA Delivery: These lipids help transport small interfering RNA (siRNA) molecules to silence target genes, supporting RNA interference (RNAi) therapies.
- Cancer Therapy: They deliver anticancer drugs to tumor cells, boosting drug efficacy while reducing off-target effects.
- Intracellular Delivery: they facilitate the transport of therapeutic molecules, such as peptides, proteins, and small molecules, into cells.
- Research Tools: Scientists use ionizable lipids to study cellular processes, explore gene functions, and develop new therapeutic strategies.
AxisPharm, a prominent global supplier of biochemicals, provides a diverse range of lipid molecules, including cationic lipids, helper lipids, and PEG lipids, to clients worldwide. Additionally, AxisPharm offers rapid and customized synthesis services for innovative lipid molecules to support your advanced research endeavors. For inquiries, please contact sales@axispharm.com.
Ref:
Han, X., Zhang, H., Butowska, K. et al. An ionizable lipid toolbox for RNA delivery. Nat Commun 12, 7233 (2021).