GalNAc (N-acetylgalactosamine) Coupling Modification Services

GalNAc technology is a targeted delivery technology based on specific chemical modifications, mainly for small nucleic acid drugs. The principle is that GalNAc has a high affinity for desialic acid glycoprotein (ASGPR), which is predominantly expressed on the surface of liver parenchymal cells. Therefore, by coupling GalNAc to small nucleic acid molecules, it helps to target binding to hepatocytes, and then the GalNAc nucleic acid couples are taken up by hepatocytes under endocytosis, achieving a high degree of liver-targeted specificity for delivery. The advantages of GalNAc delivery include subcutaneous administration, long duration of action, specificity of hepatic targeting, and low toxicity.

Fig.1 Delivery of GalNAc-siRNA conjugates into hepatocytes.(Springer et al., 2018)

Our Services

GalNAc Coupling Modification

CD Formulation has extensive experience in GalNAc coupling modification services. To improve the efficacy of GalNAc coupling with small molecule nucleic acids, our dedicated team of scientists is skilled in developing stability-enhancing chemical modification technologies to help our clients better develop and deliver drugs effectively. Specifically, N-acetylated galactosamine ((GalNAc)) is covalently coupled to different sequences of siRNA in a trivalent state to form a polysaccharide-siRNA monoadhesive for specific delivery to hepatocytes. Due to the high affinity of GalNAc for desialic acid glycoprotein (ASGPR), GalNAc binds to ASGPR on the surface of liver parenchymal cells and enters the cells to form endosomes through cellular endocytosis, thus bringing sufficient amount of siRNA into the cells to induce selective RNA silencing response. Currently CD Formulation offers custom GalNAc modified drugs mainly GalNAc-antisense nucleic acid (ASO) and GalNAc-siRNA.

Fig.2 Schemes of the Most Common Chemical Modifications Found in GalNAc Conjugates.(Debacker et al., 2020)

CD Formulation is able to provide customers with proven GalNAc delivery molecule synthesis and custom synthesis services for various modified GalNAc molecules, as well as one-stop service for GalNAc-siRNA splice synthesis.

Advantages of Our Services

• Efficient Team with on-time Delivery

CD Formulation has a highly professional and efficient R&D team. The team has employees with Master's, PhD and above degrees. CD Formulation strives to deliver on time and efficiently for our clients' projects, and is trusted by our clients.

• Advanced Laboratory Equipment

CD Formulation has advanced laboratories with complete instrumentation and facilities, and modernized process management, all of which provide a strong guarantee for the quality progress of the project.

• Advanced Technology Platform

CD Formulation has established a technology platform related to drug delivery systems, including both screening and testing platforms for compounds, which greatly improves the drug development process conducted by drug delivery technology.

About CD Formulation

CD Formulation provides integrated innovation solutions from strategy to implementation to help you increase opportunities and address challenges. Through our in-depth experience in many different industries, including consumer and technology, we bring innovative solutions and cross-industry best practices to drug development. If you have a requirement about our services, please contact us by phone or email, our colleagues will reply to you within three working days.

References

1. Springer, Aaron D., and Steven F. Dowdy. GalNAc-siRNA conjugates: leading the way for delivery of RNAi therapeutics[J]. Nucleic acid therapeutics, 2018, 28(3): 109-118.
2. Debacker, Alexandre J., et al. Delivery of oligonucleotides to the liver with GalNAc: from research to registered therapeutic drug[J]. Molecular Therapy, 2020, 28(8): 1759-1771.