Conjugations
Enhance delivery by attaching targeted ligands to guide therapeutic
oligonucleotides to specific tissues
Conjugations
Enhance delivery by attaching targeted ligands to guide RNAi molecules to specific tissues
Targeted Delivery Through Smart Design
RNAi therapeutics succeed not just by hitting the right sequence, but by delivering it to the right place. Conjugation — attaching ligands, lipids, or other functional groups to oligonucleotides — is a key tool for guiding therapeutic molecules to specific tissues, improving cellular uptake, and enhancing biological performance.
Whether you’re targeting hepatocytes with GalNAc, enhancing distribution with cholesterol, or exploring novel tissue-specific peptides, conjugations help bridge the gap between a promising sequence and real-world effectiveness.
Why Conjugations Matter
On their own, siRNAs and antisense oligos often face serious delivery challenges. They may be rapidly cleared from circulation, poorly taken up by cells, or unable to reach the intended tissue. Conjugates help address these hurdles by improving how oligos interact with their environment — both inside the body and inside the cell.
Tissue-targeting ligands like GalNAc have made liver-directed delivery highly efficient and are a mainstay in approved RNAi drugs. Lipophilic groups like cholesterol or long-chain fatty acids enhance cellular uptake and broaden biodistribution. Peptide and antibody-based conjugates allow for highly specific targeting, particularly in harder-to-reach tissues like muscle or tumors. Even more utilitarian additions like PEG or biotin can fine-tune pharmacokinetics or enable tracking and imaging during preclinical development.
These approaches often eliminate the need for complex carriers like lipid nanoparticles, offering simpler, more scalable delivery solutions — provided the conjugate is well-matched to the oligo and the therapeutic context.
Examples of Common Conjugates
- GalNAc: is the current gold standard for liver-targeted RNAi delivery. It binds efficiently to the asialoglycoprotein receptor (ASGPR), enabling highly specific and potent knockdown in hepatocytes.
- Cholesterol: increases membrane affinity, promotes endosomal escape, and supports uptake in a variety of tissues.
- Fatty acids: like DCA extend circulation time and tissue exposure by improving plasma protein interactions.
- Cell-penetrating peptides (CPPs) and antibody conjugates: enable targeted delivery beyond the liver — a growing area of exploration for muscle, CNS, and immune system applications.
- PEGylation: helps reduce immunogenicity and extend half-life, while biotin and fluorophores support research, imaging, and assay development.
How We Support Conjugate Evaluation
We help clients understand which conjugates make the most sense based on their target tissue, delivery route, and therapeutic goals. Whether you’re bringing your own conjugated oligos or need help sourcing custom chemistries, our platform allows head-to-head comparisons of uptake, potency, and durability.
Using standard assays like qPCR, western blotting, or ELISA, we assess the impact of conjugation on knockdown efficiency and cellular delivery. Our team also offers guidance on integrating conjugates with backbone modifications or optimizing linker design to ensure compatibility and function.
A Smart Sequence-First Strategy
In most cases, we recommend validating sequence activity first, then layering in delivery strategies like conjugates. This keeps early development focused and cost-effective, while ensuring that later-stage candidates benefit from targeted delivery only when it adds real value. Once conjugate performance is confirmed, we help clients introduce chemical modifications — like 2’-OMe or phosphorothioates — to enhance in vivo stability and therapeutic efficacy.
Build Smarter RNAi Delivery
Whether you’re optimizing a liver-targeted siRNA or testing new approaches for extrahepatic delivery, ADViRNA helps you make informed, data-driven decisions about conjugation strategy.
Build Smarter RNAi Delivery
Whether you’re optimizing a liver-targeted siRNA or testing new approaches for extrahepatic delivery, ADViRNA helps you make informed, data-driven decisions about conjugation strategy.