Description:
GA-Chol(glutamate-cholesterol) is a novel synthetic cholesterol derivative designed to overcome the liver tropism of conventional lipid nanoparticles (LNPs) after local administration. It is synthesized through a two-step reaction involving the covalent conjugation of glutamic acid to cholesterol. When incorporated into LNPs, GA-Chol replaces native cholesterol (typically 38.5 mol%), significantly altering the nanoparticles' properties. A key characteristic of GA-Chol LNPs is their strongly negative zeta potential, which contrasts with the nearly neutral charge of standard cholesterol-containing LNPs. This modification is crucial for altering the LNP's behavior in vivo. Following intramuscular or intratumoral injection, GA-Chol LNPs exhibit superior retention at the injection site, demonstrating robust localized transfection with minimal leakage into the systemic circulation and subsequent off-target expression in the liver. This localized retention effect is consistent across various cancer models. Furthermore, GA-Chol enhances in vitrotransfection efficiency by approximately 10 to 20-fold in different cell lines. Therapeutically, LNPs formulated with GA-Chol enable effective local delivery of potent mRNA cargoes, such as constitutively active caspase-3, achieving significant tumor growth inhibition in mouse models while mitigating risks of hepatotoxicity, showcasing its potential for targeted nucleic acid therapies.
Handling:
Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months.
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance,
we recommend that you store the solution as aliquots in tightly sealed vials at -20°C. Generally, these will be useable for up to one
month. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at
least 1 hour.