GalNAc-Based Drug Delivery System
CD Bioparticles provides high-quality synthesis of GalNAc delivery molecules that are key to enabling hepatocyte-targeted drug delivery. In addition, we also provide customized GalNAc molecules with various modifications that can enhance drug delivery efficiency, specificity or stability to meet specific customer needs.
Introduction to GalNAc
GaINAC (N-acetylgalactosamine) is a high affinity targeting ligand for the desialylate glycoprotein receptor (ASGPR). ASGPR is an ideal receptor for active targeting, which is specifically highly expressed on the surface of hepatocytes. When bound to GalNAc, it enters into the cell to form endosomes through cellular endocytosis, thus bringing sufficient amount of nucleic acid drugs into the cell to realize liver-targeted delivery of nucleic acid drugs.GaINAc is currently mainly applied to the delivery of siRNA or ASO, and it can form a concatenation with siRNA or ASO drugs to take advantage of the specific expression of GaINAc to hepatocytes. ASGPR to precisely deliver drugs to the liver.
Figure 1. Schematic representation of GaINAC-mediated delivery of SiRNA and ASO to hepatocytes. (Cui H, et al.; 2021)
Based on the GalNAc delivery technology, the first product was approved for marketing in 2019. Up to now, 4 GaINAC-siRNA conjugates have entered the market, with Alnylam involved in the development and promotion of all products. The structure of these four GalNAc-siRNA conjugates consists of three parts: a triantennary GalNAc targeting head, a linker arm, and the siRNA molecule. GalNAc is covalently conjugated in a triantennary form to the 3' end of the sense strand of siRNA, forming a GalNAc-siRNA conjugate.
Table 1 Products based on GalNac delivery technology.
| RNA Type | Drug Name | Active Ingredient | Target | Indication | Approval Year | GalNAc Type |
|---|
| siRNA | Givlaari | Givosiran | ALAS1 | Acute hepatic porphyria | 2019 | L96 |
| Oxlumo | Lumasiran | HAO1 | Primary hyperoxaluria type I | 2020 | L96 |
| Leqvio | Inclisiran | PCSK9 | Hypercholesterolemia | 2020 | L96 |
| Amvuttra | Vutrisiran | hATTR | hATTR amyloidosis | 2022 | L96 |
Advantages of the GalNAc Drug Delivery System
- Subcutaneous injection achieves excellent drug distribution and long duration of action.
- Highly efficient targeting delivery to the liver, low toxicity and side effects, low drug dosage required.
Our Service
- Synthesis of custom-modified GalNAc molecules
- Synthesis of GalNAc-siRNA conjugates
In addition, we also provide a variety of GalNAc delivery molecules products.
For more information on GalNAc products, click here.
Our Advantage
- High purity ingredients: We rigorously select the highest quality ingredients to ensure the purity and potency of our products
- Higher loading capacity for CPG and PS than most other companies
- Technical support: Our products are based on the latest scientific research to ensure you get the best health benefits
- Competitive price
CD Bioparticles is an expert in GalNAc drug delivery with many years of experience. We can provide customers with mature services for the synthesis of GalNAc delivery molecules, custom synthesis of various modified GalNAc molecules, and one-stop services for the synthesis of GalNAc-siRNA conjugates. Among them, the synthesis scale of GalNAc delivery molecules ranges from grams to kilograms.
Reference
- Cui H, et al.; Liver-targeted delivery of oligonucleotides with N-Acetylgalactosamine conjugation. ACS Omega. 2021, 6:16259-15265.
