ALC-0159

Methoxypolyethyleneglycoloxy(2000)-N,N-ditetradecylacetamide or ALC-0159, is a methoxypolyethylene glycol (PEG-2000) conjugated lipid and is designed to enhance the stability and biocompatibility of LNP drug delivery systems.

By forming a hydrophilic shield, ALC-0159 significantly reduces immune recognition to increase circulation time and improve bioavailability. As a key component in mRNA-based vaccines, this PEGylated lipid carries out a fundamental function in efficient nanoparticle encapsulation and intracellular delivery. This makes it indispensable in cutting-edge pharmaceutical and gene therapy applications.

ALC-0159 is a foundational element in LNPs for mRNA-based vaccines, including COVID-19 formulations. It is also vital for stabilizing nanoparticle formulations in nucleic acid and small-molecule drug delivery.

Other notable applications include its ability to improve stability, bioavailability, and reduced immunogenicity in CRISPR, siRNA, and antisense oligonucleotide uses, as well as driving next-generation RNA-based therapies, which enables improved systemic circulation and controlled release.

ALC-0159 is a polyethylene glycol (PEG)-lipid conjugate also called a PEGylated lipid. ALC-0159 is a lipid excipient that can be used to form lipid nanoparticles (LNPs).

Polyethylene glycol (PEG)-lipids have been the polymer-lipid conjugate of choice for lipid formulations for decades. PEG-lipids are used increase systemic circulation times, mediate indirect targeting capabilities, promote LNP self-assembly, control size and aid in storage stability. Particles containing PEG-lipids are able to bypass the reticulo-endothelial system, giving them their nickname - “stealth agents”.  ALC-0159 is not a traditional phospholipid as it contains two saturated 14-carbon chains joined at a nitrogen atom which is then linked to the poly(ethylene glycol).

Functions include:
- Increased half life when administered systemically

- Aids in storage ability

- Helps obtain small particle sizes