Chemical modifications and molecular conjugations are essential components of small nucleic acid design, enabling the optimization of molecular stability, affinity, and functional properties. In small nucleic acid applications such as siRNA and ASO, different modification types and combinations can directly influence the physicochemical properties and functional performance of molecules. Therefore, robust and reliable modification synthesis capabilities are critical for producing high-quality small nucleic acids.
With 15+ years of specialized oligonucleotide synthesis experience and proprietary modification technologies, BiOligo provides access to 200+ chemical modifications, including 2′-O-methyl, 2′-Fluoro, PS, EVP, DCA, LNA, and SP18 (PEG6), as well as diverse conjugation solutions such as GalNAc, lipids, peptides, small molecules, and antibodies.
Modification Types
Leveraging a mature oligonucleotide synthesis platform, BiOligo provides access to 200+ modifications across sugar, backbone, base, and labeling modifications. These modifications can be introduced at different positions and combined flexibly to meet diverse small nucleic acid design requirements.
Common Modification Options
Conjugation Types
The in vivo efficacy of small nucleic acid therapeutics (siRNA, ASO, and RNAi-based drugs) largely depends on the availability of efficient, stable, and tissue-specific delivery systems. Current leading targeted delivery strategies include GalNAc-mediated delivery for liver targeting, antibody–oligonucleotide conjugates (AOCs) for extrahepatic targeting, and various conjugation approaches using small molecules and functional ligands.BiOligo provides diverse conjugation solutions, including GalNAc, antibodies (AOCs), peptides, and small molecules, with comprehensive support for scalable synthesis and production.
GalNAc Delivery Platform
GalNAc (N-acetylgalactosamine) conjugation technology is one of the most clinically advanced and widely used liver-targeted delivery strategies for small nucleic acid therapeutics.By specifically binding to the asialoglycoprotein receptor (ASGPR) expressed on hepatocytes, GalNAc conjugates enable efficient and selective uptake by liver cells, thereby significantly enhancing the in vivo gene silencing efficiency of siRNA and ASO therapeutics.
AOC Antibody–Oligonucleotide Conjugation Platform
Antibody–oligonucleotide conjugates (AOCs) represent an emerging targeted delivery strategy that enables precise delivery of small nucleic acid therapeutics to extrahepatic tissues by conjugating tissue-specific monoclonal antibodies with oligonucleotide drugs.This approach overcomes the limitations of conventional liver-targeted delivery strategies and shows significant potential for applications in muscle, oncology, and other difficult-to-transfect tissues.
Antibody — Enables tissue- or cell-specific targeting
Linker — Determines conjugation stability and payload release characteristics
Nucleic Acid Payload (siRNA / ASO) — Mediates gene silencing or RNA modulation
Conjugation Chemistry Strategies
BiOligo supports multiple AOC conjugation strategies and provides flexible conjugation development and optimization services tailored to antibody structure, payload type, and desired product homogeneity.
Conjugation Strategy Key Features Homogeneity Common Chemistries Application Characteristics Random Lysine Conjugation Random modification of surface lysine residues on antibodies Low NHS Ester Mature chemistry and rapid development Random Cysteine Conjugation Conjugation through native or reduced cysteine residues Moderate Maleimide High conjugation efficiency Site-Specific Cysteine Conjugation Precise conjugation through engineered or selected cysteine sites High Maleimide / Click Chemistry Controlled DAR and improved consistency Fc Glycan Site-Specific Conjugation Modification through Fc-region glycans High Glycan Remodeling Minimal impact on Fab function Enzymatic Site-Specific Conjugation Enzyme-mediated conjugation using specific recognition sites High Sortase / Transglutaminase Highly specific development Engineered Site-Specific Conjugation Introduction of defined conjugation sites through genetic engineering Very High Non-natural Amino Acids / Click Chemistry Advanced precision conjugation platforms
