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GalNAc-siRNA Conjugate Development

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CD Formulation is committed to providing expert and precise GalNAc-siRNA splicing solutions to our global customers. We offer custom chemical modifications and ligation techniques to ensure the stability of GalNAc-siRNA. Our comprehensive service is designed to fully support the development and production of GalNAc-siRNA conjugate.

What is GalNAc-siRNA Conjugate?

GalNAc-siRNA conjugates are polysaccharide-siRNA complexes with N-acetylated galactosamine (GalNAc) at their 5' ends. By targeting the asialoglycoprotein receptor (ASGPR), GalNAc enables high selectivity and rapid internalization into hepatocytes, enhancing specificity. This modification is the leading small nucleic acid pharmacophore and shows promise for treating hepatic diseases related to gene overexpression, having largely replaced lipid nanoparticle (LNP)-based delivery systems in liver-targeted therapies.

Fig.1 GalNAc-siRNA conjugates structure. Fig.1 Structure of GalNAc - siRNA conjugates. (Kanasty R, et al., 2013)

Explore Our GalNAc-siRNA Conjugate Development Services

Custom GalNAc-siRNA Conjugate Synthesis Services

As a synthesis service provider for GalNAc-siRNA conjugates, CD Formulation provides reliable and precise conjugates for research and development. To ensure that each siRNA is synthesized to the highest standards, we utilize advanced synthesis technologies and rigorous quality control processes.

Chemical Optimization Services of GalNAc-siRNA Conjugates

Services	Descriptions
Backbone Modification Services	2'-F and 2'-OMe modifications at the 2' end of siRNA significantly increase its stability and reduce its susceptibility to degradation by RNA enzymes. The modifications exhibit similar biophysical properties as the natural 2'-OH sequence, and they are well tolerated by the TAR RNA-binding protein.
End Modification Services	When siRNA is modified with thio-phosphates at the 5' and 3' ends, the efficiency, stability, and longevity of RNA interference (RNAi) in vivo are improved significantly. This approach closely resembles the strategies employed to optimize the stability of antisense oligonucleotides (ASOs).

GalNAc-siRNA Characterization Services

To ensure the safety and efficacy of GalNAc-siRNA, we evaluate its physical, chemical, and biological properties.

Services	Descriptions
Particle Size and Morphology Analysis	The particle size distribution and morphology of the affixes are evaluated using DLS and TEM.
Surface Charge Determination	The detection of surface charge using the zeta potential technique is essential for understanding its stability in biological environments.
Structure Analysis	Determine the chemical structure and molecular weight using MS and NMR technologies to ensure the integrity and purity of the compounds.
Stability Testing	Evaluate the protective effects of GalNAc modifications on siRNAs under various environmental conditions to ensure their integrity and activity throughout the in vivo cycle.

General Workflow for GalNAc-siRNA Conjugate Development Services

Fig.2 Workflow for GalNAc-siRNA conjugates development. Fig.2 Flow chart of GalNAc-siRNA conjugate development. (CD Formulation)

siRNA Synthesis

The preparation of siRNA strands in the laboratory involves chemical synthesis methods that may include specific modifications to enhance stability and potency, such as 2'-F and 2'-OMe modifications.

GalNAc Ligands Synthesis

The synthesis of GalNAc monomers or polymeric structures suitable for siRNA attachment, along with the necessary chemical modifications to GalNAc, is essential for enhancing its binding affinity to siRNA and improving delivery efficiency.

Affixation of siRNA to GalNAc

Covalent or non-covalent attachment of synthesized siRNA to a GalNAc ligand through chemical linkage.

Identification of Conjugates

Identify the chemical structure and molecular weight of the compound using MS, NMR, and other analytical techniques.

Evaluation of Physicochemical Properties

Evaluate the particle size and morphology of the adducts using DLS, TEM and other methods.

Advantages of Our GalNAc-siRNA Conjugate Development Services

We offer chemical modifications like 2'F, 2'OMe, 2'MOE, LNA, cEt, 5'VP, PS, and PO to enhance the stability and affinity of GalNAc-siRNA conjugates.
We offer customized services to design and develop GalNAc-siRNA conjugates tailored to our clients' research and application needs.
We offer analytical support with a skilled team to ensure the project's smooth progress.

Our Technology Platforms

Platforms	Descriptions
Synthesis Platform	Solid-phase synthesis technology for siRNA synthesis and chemical modification.
Analytical Technology Platform	HPLC, MS and NMR are utilized to characterize the chemical structure, purity, and molecular weight of GalNAc-siRNA conjugates.

Published Data

Technology: GalNAc-siRNA conjugate utilizes chemical synthesis technology

Journal: Genes

IF: 4.141

Published: 2018

Results:

Antisense oligonucleotides (ASOs), siRNAs, and miRNAs have effectively reduced abnormal protein levels and restored noncoding RNA (ncRNA) levels linked to diseases like cancer by targeting messenger RNAs (mRNAs). In addition to formulation approaches that help accelerate the use of ASOs, siRNAs, and miRNAs in clinical trials, covalent linkage between nonviral vectors and nucleic acids brings new value and promise for the development of promising nucleic acid therapeutics.

Fig.3 Schemes of GalNAc-siRNA conjugates. Fig.3 Schemes of siRNA conjugates containing GalNAc. (Grijalvo S, et al., 2018)

CD Formulation's custom synthesis service for GalNAc-siRNA delivers high-quality and efficient solutions. Contact us, we'll support your R&D projects.

References

Kanasty R, Dorkin J R, Vegas A, et al. Delivery materials for siRNA therapeutics. Nat. Mater. 2013, 12(11): 967-977.
Grijalvo S, Alagia A, Jorge A F, et al. Covalent strategies for targeting messenger and non-coding RNAs: an updated review on siRNA, miRNA and antimiR conjugates. Genes. 2018, 9(2): 74.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.

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