Description:
AA76-lipid is a dipeptide-modified ionizable lipid, engineered with an arginine-histidine motif, that constitutes the core of the pancreatic-targeted AH-LNP delivery platform. Its chemical architecture, characterized by an externally positioned and C-terminally modified arginine residue, was identified through systematic screening as the optimal structure for function. Upon intraperitoneal administration, AH-LNPs formulated with this lipid interact with proteins in the peritoneal fluid, undergoing dynamic assembly into significantly larger complexes. This substantial increase in size (from ~100 nm to over 360 nm) exploits a physical targeting principle termed the Capsule-filter-mediated pancreatic targeting (CAMP) mechanism. Large particles are selectively filtered out by the dense capsules of other abdominal organs, leading to preferential enrichment in the capsule-deficient pancreas. Concurrently, the arginine-histidine motif directs the formation of a distinct protein corona enriched with apolipoproteins (e.g., APOE, APOB-100), which mimics very-low-density lipoprotein (VLDL). This corona enables efficient cellular internalization primarily into pancreatic stromal cells via VLDL receptor (VLDLR)-mediated endocytosis, known as the VMP pathway. The synergistic integration of the physical CAMP targeting and the biological VMP uptake mechanisms empowers AA76-lipid-based AH-LNPs to achieve highly specific, potent, and sustained mRNA delivery and gene editing within the pancreas across multiple species, demonstrating exceptional therapeutic efficacy in models of both autoimmune pancreatitis and pancreatic cancer.
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.