N-Acetylgalactosamine (GalNAc)
Short-interfering RNA (siRNA)-induced RNA interference (RNAi) responses have great potential to treat a wide variety of human diseases. A number of N-acetylgalactosamine (GalNAc)-siRNAs as RNAi therapeutics are currently in various stages of development. Creative Biolabs has accumulated extensive experience in offering our global clients with high-quality conjugation service of GalNAc-siRNA. Chemical modifications can be introduced to enhance the stability of GalNAc-siRNA.
GalNAc-mediated siRNA Delivery
Oligonucleotide-based drugs are emerging as an important class of human therapeutics due to their ability to harness natural cellular mechanisms. These drugs have the ability to silence the synthesis of disease-associated proteins by intervening at the transcript level. Of the various classes of oligonucleotide-based therapies, siRNAs are the most clinically advanced oligonucleotide-based platforms. Directly conjugating siRNAs to a triantennary GalNAc sugar, targeted delivery to liver hepatocytes has been achieved, for receptor-mediated endocytosis via the asialoglycoprotein receptor (ASGPR) which is primarily expressed on the surface of hepatocytes. GalNAc-siRNA conjugates are a simple solution to the siRNA delivery problem for hepatocytes and have shown the RNAi field the path forward for targeting other tissue types. This siRNA delivery system has been used successfully in nonclinical species and in humans to suppress the expression of many hepatocellular target RNAs. Furthermore, GalNAc-siRNAs are a promising class of oligonucleotide-based therapeutics with the potential to impact hepatic infectious diseases by targeted knockdown of disease-causing RNAs, rare genetic diseases, and cardiometabolic diseases.
Figure 1. Structure of the triantennary GalNAc–siRNA conjugate. (Kanasty, 2013)
Service
With years of research and development experience in RNAi, Creative Biolabs has owned a group of scientists who are proficient in the preparation of GalNAc-siRNA conjugations. In order to improve the efficacy of GalNAc-siRNA conjugates, our scientists are skilling in introducing chemical modifications that provide enhanced stabilization. We are confident in providing high-quality service to facilitate our clients' GalNAc-siRNA therapeutics development.
Highlights
- Chemical modifications can be introduced.
- GalNAc-siRNA with well-tolerated in toxicology study.
- GalNAc-siRNA with enhanced stabilization chemistry.
- GalNAc-siRNA with high therapeutic indices, efficacy, and duration of action.
Owing to their high predicted therapeutic indices and duration of action, GalNAc-conjugated RNAi therapeutics have the potential to have a major impact in a variety of patient populations with high unmet need. In terms of the extensive experience in RNAi research, Creative Biolabs is proud to offer our clients with custom GalNAc-siRNA conjugations service. For more detailed information, please feel free to contact us or directly send us an inquiry.
Reference
- Kanasty, R.; et al. (2013). Delivery materials for siRNA therapeutics. Nat Mater. 12(11):967-77
