Antibody-siRNA Conjugation (ARC)

* Please kindly note that our services can only be used to support research purposes (Not for clinical use).

As a leading CRO, BOC Sciences is dedicated to providing custom conjugation services to clients at the forefront of drug conjugation. With the FDA approval of several siRNA drugs, the development of siRNAs has attracted significant attention from researchers, where the design of delivery systems for siRNAs is a key issue for further clinical applications. Therefore, antibody-siRNA conjugates (ARCs) have emerged as potential carriers for targeted siRNA drug delivery. We are able to provide antibody-siRNA conjugation services to meet your unique project needs. Our scientific team will work with you to create a scope of work to complete the project on time and within specifications.

Find out more with Drug Conjugation Services.

Introduction of siRNA

Small interfering RNA (siRNA) is a kind of macromolecular drugs with a molecular weight of approximately 13 kDa belonging to a family of small non-encoding ribonucleic acid (sncRNA). siRNAs, as double-stranded RNAs, suppress protein translation by recruiting RNA-induced silencing complex (RISC) to mRNA via Watson-Crick base pairing. siRNAs can target and silence aimed gene expression such as oncogenes, tumor suppressor genes and other regulatory genes by specific sequence recognition with mRNA. Despite advances siRNA-based therapies, low delivery efficiency and limited bio-barriers penetrability (owing to its strong negative charge and hydrophilic property) appear to be major obstacles for targeted siRNA therapeutics.

Introduction of ARC

Antibody-siRNA conjugate (ARC), an emerging siRNA drug delivery strategy, can overcome the current barriers in siRNA delivery. Inspired by the concept of ADC , ARC consists of the ligand (antibody) and the warhead (siRNA). ARCs can be produced by conjugating siRNA directly with multiple chemical groups in the antibody. Classical ARCs are prepared mainly based on the natural lysine residues in natural antibody or the cysteine residues reduced from the interchain disulfide bonds. Common conjugation methods involved in ARCs include Sulfhydryl and maleimide reaction, Amino and β-lactam ring-opening reaction, Biotin and avidin affinity reaction, etc. In addition, the antibody and siRNA also can be combined through electrostatic interactions, which has not been as widely used as chemical conjugation methods.

Antibody directly  conjugated to siRNA Fig 1. Antibody directly conjugated to siRNA (Paunovska, 2022)

Our Services

  • Selection and screening of ligands
  • Site-specific chemical modification of siRNA
  • Optimization of conjugation methods and linkers
  • Antibody-siRNA conjugation

Examples of antibody-siRNA conjugates:

LinkerAntibody/Fragment typesiRNAApplication
Sulfhydryl-maleimideAnti-CD71 Fab fragmentApoB, HPRT, myostatin siRNAMuscle diseases therapy
THIOMABsiGenome HPS4-3, OTP HPS4-8 siRNADelivery system
Amino + β-lactam ringHumanized DVD-IgGHuman β-catenin (CTNNB1) siRNADelivery system
Avidin-biotinHeavy chain variable region (VH) of 2C10tNASP siRNAAnti-mammal cancer
Polyclonal IgG-targeting antibodyNephrin siRNA, TRPC6 siRNAPodocytes-injured glomerular diseases treatment
Anti-human insulin receptor antibodyAnti-luciferase siRNAAnti-cancer siRNA delivery system
Poly-lysineRGD peptideAnti-luciferase siRNAAnti-tumor siRNA delivery

Applications of ARC

Antibody-mediated siRNA delivery systems can be a promising choice. For example, siRNAs have been delivered to extrahepatic tissues using ARCs. These conjugates with low immunity can achieve pretty therapeutic effects and their simple prepare process make them closer to clinical transform.

siRNA has great application prospects in treatments of varies diseases. siRNAs can be conjugated with antibodies for treating cancer such as breast cancer, prostate cancer, colon cancer, or other diseases such as HIV and leukemia.

Our Advantages

  • Different ARC structures and batch development experience
  • Various conjugation methods through chemical modification or noncovalent interactions
  • A wide range of characteristic analysis
  • People and suites that specialize in ARC development, manufacturing, and testing
  • Data analysis, detailed report with results and discussion
  • Cost-effective and high-quality products

References

  1. Cao, W., et al., Antibody-siRNA conjugates (ARC): Emerging siRNA drug formulation, Medicine in Drug Discovery, 2022, 15, 100128.
  2. Paunovska, K., Loughrey, D., and Dahlman, J. E., Drug delivery systems for RNA therapeutics, Nat. Rev. Genet., 2022, 23, 265-280.

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