CDD Vault Update (March 2026): siRNA Composition and Registration

CDD Vault now enables registration, annotation, and structure generation for siRNA molecules, including support for duplexes, hairpins, strand breaks, and complex conjugated chemistries. This enhancement provides a chemically precise and visually accurate representation of siRNA constructs within Vault.

What's new in this release:

• Register full siRNA duplexes with exact chemical structure
• Define hydrogen bonding (base pairing) explicitly
• Annotate backbone breaks and structural features
• Register shRNA and dumbbell constructs
• Incorporate custom monomers and conjugates
• Import siRNA directly from tabular data files

siRNA Composition During Import

Compose siRNA directly from Sense and Antisense (5'–3') sequence columns using the Data Import workflow.

Minimum Requirements:

• One column for Sense (5'–3')
• One column for Antisense (5'–3')
• Sequences must be provided in 5'–3' orientation

During import:

1. Select Compose macromolecules from columns
2. Choose siRNA
3. Map Sense and Antisense strands
4. Optionally cleave 5' terminal phosphates
5. Select DNA or RNA backbone behavior for natural bases

A Molfile is automatically generated and mapped to the Structure field.
Inclisiran:

Explicit Base Pair Annotation
Define hydrogen bonding using pairing block syntax for precise duplex control, including support for anchor-based and individual base-pair annotations.

Syntax = Sequence{@Start-End:ID}

Where:

• @ indicates hydrogen bond annotation
• Start-End defines the pairing range
• :ID links complementary pairing blocks across strands

This allows for precise duplex definition, support for reversed antisense numbering, and multiple pairing blocks per strand.

Backbone Breaks and Hairpins

Annotate nicked strands, internal loops, and terminal hairpins (shRNA and dumbbell structures).

• Nicked strands: depicted by inserting a period (.) between the desired monomers

• Internal loops: use multiple Pairing Block IDs to jump over the unpaired monomers

• Terminal hairpins: use the Loop Operator {&:ID} in addition to the annotations described above (pictured below)

Custom Monomer Support
Incorporate registered custom monomers and conjugates (e.g., modified sugars, GalNAc) directly within sequences. Use a square bracket notation in the sequence to identify the custom monomer. CDD Vault will automatically resolve custom monomers from your monomer library, apply the registered backbone chemistry, and incorporate them into the generated structure.

These enhancements expand Vault’s support for oligonucleotide therapeutics, providing chemically rigorous registration and visualization of complex siRNA modalities.

For more detailed information please see the linked Knowledge Base Article here.

To provide feedback on features, or if you have questions and want to schedule a demo, please contact support@collaborativedrug.com.