At BOC Sciences, we specialize in custom GalNAc-siRNA conjugate synthesis and design to support your liver-targeted RNAi research and drug development. Leveraging our deep expertise in nucleic acid chemistry and delivery systems, we offer end-to-end services including GalNAc-siRNA design optimization, chemical conjugation, and in vitro/in vivo validation. Our scalable platform enables high-purity, ready-to-use conjugates for effective ASGPR-mediated siRNA delivery to hepatocytes, eliminating the need for lipid nanoparticles. Whether you're validating gene targets, conducting preclinical studies, or advancing RNA therapeutics, our GalNAc-siRNA conjugation service ensures precise, reliable, and efficient liver-specific gene silencing. Partner with us to accelerate your RNAi research with confidence.
Liver-targeted siRNA delivery: GalNAc-siRNA enables highly efficient and specific delivery of siRNA to hepatocytes via the ASGPR receptor. This reduces off-target effects and improves therapeutic outcomes for liver-related diseases.
Enhanced in vivo stability of siRNA: By conjugating GalNAc to siRNA, the molecule gains improved stability in the bloodstream. This ensures longer circulation time and stronger gene knockdown effects in vivo.
Elimination of lipid nanoparticles (LNP): GalNAc-siRNA conjugates do not require LNPs or viral vectors, simplifying the delivery process. Researchers can achieve efficient siRNA delivery with fewer toxicity concerns.
Easy subcutaneous administration: These conjugates allow for non-invasive subcutaneous injection, enabling straightforward in vivo studies. This makes GalNAc-siRNA ideal for both preclinical and translational research settings.
Accelerated target validation: GalNAc-siRNA is a powerful tool for gene function studies in liver tissue, supporting rapid target validation in drug discovery. It helps researchers quickly assess the role of disease-related genes.
Scalable for therapeutic development: As a clinically validated platform used in FDA-approved drugs, GalNAc-siRNA offers a scalable and reproducible path to RNAi therapeutics. This makes it highly suitable for pharma and biotech R&D pipelines.
BOC Sciences offers a wide spectrum of GalNAc-siRNA conjugates services including design, synthesis, characterization and preclinical evaluation. This platform utilizes cutting-edge nucleic acid chemistry and drug delivery technologies provided by our multidisciplinary team of experts to develop customized, individually tailored GalNAc-siRNA conjugates unmatched in precision and efficacy. Our end-to-end solutions from target selection through to preclinical validation provide clients the agility and efficacy required to accelerate their RNA therapeutic programs.
Here, we start our journey by focusing on thoughtfully engineered strategies to enhance the potency, specificity, and stability of GalNAc-siRNA conjugates. Using cutting-edge computational modeling and structural biology techniques, our team is able to determine target genes, and logically infer the siRNA sequences optimal for silencing a particular disease-associated transcript. We further iterate on the chemical structure and conjugation strategy of GalNAc-siRNA conjugates to hone in on the right balance of therapeutic efficacy and safety.
As an expert in synthetic chemistry and nucleic acid synthesis, BOC Sciences has a strong synthetic strength that allows to synthesize GalNAc-siRNA conjugates with efficient and accurate selective chemical composition and purity. With those aforementioned synthesis platforms, we can manufacture conjugates of the highest quality at scale and sufficient to support discovery and development preclinical. Rigorous quality control measures ensure the integrity and reproducibility of synthesized GalNAc-siRNA conjugates, laying the foundation for reliable therapeutic outcomes.
GalNAc-siRNA conjugates must be well characterized in view of their physicochemical properties, stability, and pharmacokinetic profiles for evaluation. We use mass spectrometry, high-performance liquid chromatography (HPLC), and gel electrophoresis to characterize the synthesized conjugates comprehensively at BOC Sciences. Through defining critical quality attributes such as conjugate purity, molecular weight and binding affinity, we confirm the strength and reliability of GalNAc-siRNA conjugates across a range of formulations and lots.
Safety, efficacy, and pharmacokinetic evaluation of novel GalNAc-siRNA conjugates are carried out using preclinical rodent studies prior to translation into humans. Furthermore, BOC Sciences can provide a series of Preclinical Services, such as in vitro cell-based assays, animal pharmacokinetics studies, and efficacy evaluations in disease models.
Our GalNAc-siRNA service follows a streamlined, milestone-driven workflow designed to ensure precision, quality, and fast turnaround. Here's how we work with you, step by step:
Our experts discuss your project goals, target gene(s), species, and delivery strategy. We assess feasibility and recommend optimal siRNA designs for liver-targeted RNAi studies.
We design and/or optimize siRNA duplexes with chemical modifications (e.g., 2'-OMe, 2'-F, PS linkages) to enhance stability, reduce immunogenicity, and improve silencing efficacy.
Both strands of the siRNA are chemically synthesized under stringent quality controls. Optional purification via HPLC or PAGE ensures high purity for research-grade applications.
We conjugate a triantennary GalNAc ligand to the siRNA (typically 3' end of the sense strand), enabling ASGPR-mediated liver targeting upon subcutaneous administration.
Every batch undergoes full QC, including MALDI-TOF MS, HPLC profiles, and endotoxin testing. You receive a detailed Certificate of Analysis (CoA) with shipment.
Keyword: in vivo siRNA gene knockdown testing
Upon request, we offer in vitro transfection and gene silencing studies, or formulation of conjugates for mouse/rat liver-targeted studies. This accelerates preclinical proof-of-concept.
Your GalNAc-siRNA is delivered lyophilized or in buffer, with full documentation and usage guidelines. Ongoing technical support ensures smooth downstream applications.
GalNAc-siRNA conjugates are widely used in liver-targeted gene silencing applications, making them essential tools in both basic research and therapeutic development. Below are the key application domains:
Figure 2. H&E staining of liver sections collected at necropsy. (Janas, M.M.; et al, 2018)
Small interfering RNAs (siRNAs) with trivalent N-acetylgalactosamine (GalNAc) ligand are under investigation in clinical trials for diverse indications. The selection process involves assessing the toxicity of lead compounds in rats at exaggerated doses. GalNAc-siRNAs exhibiting rat hepatotoxicity are excluded from further clinical development. This case focuses on investigating and addressing rodent hepatotoxicity associated with GalNAc-conjugated siRNAs selection. Rats were exposed to supratherapeutic doses of GalNAc-conjugated siRNAs. Evaluation focused on hepatotoxicity mechanisms, including RNAi-mediated off-target effects, chemical modifications, and disruption of RNAi pathways. Seed-pairing modulation with a thermally destabilizing chemical modification was employed to mitigate off-target effects. Rodent hepatotoxicity primarily stemmed from RNAi-mediated off-target effects rather than chemical modifications or RNAi pathway disruptions. Modulating seed-pairing using a thermally destabilizing chemical modification significantly enhanced the safety profile of GalNAc-siRNAs in rats. RNAi-mediated off-target effects contribute substantially to rat hepatotoxicity associated with GalNAc-conjugated siRNAs. Modulating seed-pairing with a thermally destabilizing chemical modification offers a promising strategy to mitigate off-target effects and enhance safety. This approach may reduce the occurrence of hepatotoxic siRNAs across different species, thus improving the safety profile of GalNAc-conjugated siRNAs for clinical development.
GalNAc-siRNA conjugates represent a truly novel class of RNA therapeutics enabling liver hepatocyte-specific delivery of small-interfering RNA (siRNA) payloads at an unprecedented level of efficacy. In vitro, and also in vivo,GalNAc conjugated multivalent siRNA is more potent than siRNA alone and theoretically at about the same concentrations of GalNAc could dose about 10x less of siRNA when given as just siRNA in a water-soluble delivery vehicle. The GalNAc-siRNA conjugates have therefore provided a convenient means for siRNA drug delivery to the liver and have significantly enhanced tissue-specific delivery and efficacy in ASO and siRNA therapeutics. Encapsulated in cleverly designed N-acetylgalactosamine (GalNAc) conjugates, which specifically target the highly expressed Asialoglycoprotein receptor (ASGPR) of hepatocytes, these conjugates offer great promise for the treatment of a variegated spectrum of diseases ranging from metabolic disorders, to viral infections and beyond.
The role of GalNAc, N-acetylgalactosamine, is extensively described for most species in biology. Used to glycendate proteins commonly These additions are capable of altering the structure and function of proteins to regulate cellular signaling, adhesion, and various other central cellular processes. GalNAc also functions in a range of important biological processes from cell-to-cell recognition, immune response to development.
The receptor for GalNAc is the asialoglycoprotein receptor (ASGPR). It is primarily found on the surface of hepatocytes (liver cells). ASGPR specifically recognizes and binds to glycoproteins containing terminal galactose or N-acetylgalactosamine residues. This receptor plays a crucial role in the clearance of glycoproteins from the circulation and in the internalization of certain therapeutic agents targeted to the liver.
siRNA drugs are a group of drugs that use siRNAs. Such molecules are able to be tuned to target the expression of specific genes of interest, and thereby have the potential to over ride related disease pathologies. SiRNA therapeutics accomplish the repression of genes encoding disease targets, at the post-transcriptional level, by engaging the RNA interference (RNAi) pathway, thereby diminishing or abating the pathological consequences of their overexpression.
No, GalNAc is not a glycosaminoglycan (GAG) No, it actually a monosaccharide, N- acetylgalactosamine. These proteoglycans, or matrix proteins with covalently bonded sugar chains, are made up of glycosaminoglycans or unbranched polymeric chains of repeating disaccharide units, each amino sugar with an uronic acid. GAGs also play a role in the ECM where they are constituents and modulators of biological processes such as cell signaling, tissue morphogenesis, and lubricating articulations.
A GalNAc-siRNA conjugate is a form of a GalNAC-siRNA in which the GalNAc molecule is linked to the siRNA molecule, usually at the 3′ end of the sense strand. This conjugate allows specific binding to hepatocytes because GalNAc attaches to asialoglycoprotein receptor on their cell surface. The siRNA molecule is composed of a double-stranded form of RNA, with the antisense strand guiding mRNA cleavage or translational repression by the RNA-induced silencing complex..
GalNAc binds to the asialoglycoprotein receptor (ASGPR). This receptor is predominantly found on the surface of hepatocytes (liver cells). ASGPR specifically recognizes and binds to glycoproteins containing terminal galactose or N-acetylgalactosamine (GalNAc) residues. This interaction plays a crucial role in the clearance of glycoproteins from the circulation and in the internalization of certain therapeutic agents targeted to the liver
Ready to Accelerate Your Liver-Targeted RNAi Research?
Whether you're validating a gene target, advancing an RNA therapeutic, or exploring liver-specific delivery strategies, our GalNAc-siRNA conjugation service offers the precision, quality, and support you need. Backed by expert scientists and full-spectrum customization, we help you move from concept to functional results-faster.
Contact us today for a free consultation or request a custom quote. Let's bring your RNAi ideas to life with confidence.
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