Overview

• High throughput synthesis for lead identification and lead optimization of oligonucleotide therapeutics
• Chemically modified oligonucleotides and conjugates to support Structure–Activity Relationship (SAR) studies
• Chemical synthesis of long RNA (up to 150 nucleotides)
• Organic synthesis lab

High throughput synthesis for lead identification and lead optimization – siRNAs, ASOs etc.

• Sequences received either through in-house bioinformatics in silico studies or from collaborating partners
• Synthesis of oligonucleotides in 96-well plate format with a synthesis scale up to 1 µmol
• In-house column packing system for custom CPGs (incl. ligand-based CPGs) 
• Large variety of chemical modifications available
• Ligand conjugation in high-throughput synthesis mode, e.g., GalNAc, cholesterol  
• Automation of HPLC-related purification processes (AEX, RP, SEC)
• Single strands as well as duplexes undergo QC evaluation 
• Samples delivered in screw cap vials or 96-well plate (in a custom layout) 
• siRNAs or ASOs with linkers for further conjugation delivered in 96-well plates 
• High quality and fast turnaround 

Chemically modified oligonucleotides and conjugates to support Structure–Activity Relationship (SAR) studies

• Wide range of chemically modified building blocks and site-specific functionalisation
• Site-specific backbone modification (e.g., Phosphorothioates (PS), Phosphorodithioates (PS2), (PNdmi), etc.)
• Different fluorophores
• Conjugates based on small molecules, varied peptides (incl. cationic), varied lipids and carbohydrates (e.g., GalNAc), protein conjugation (e.g., nucleic acid conjugation to BSA, KLH etc.)  
  
  • Incorporation through solid phase synthesis
  • Incorporated also through post-synthetic conjugation
  • Various conjugation strategies and chemistries amenable to ligand modification
  • Both terminal and internal modifications
• Incorporation of customer-specific modifications possible
• Spiegelmer synthesis
• Aptamer synthesis
• Oligonucleotides with 5’-Triphosphate and 5’-Diphosphate

Synthesis of long RNA

• Chemical synthesis of RNA with up to 150 nucleotides
  
  • Peptide conjugates
  • RNAs with 5’-Triphosphate or 5’-Diphosphate
• Single guide RNAs for CRISPR/Cas applications
• Aptamer synthesis
• High yields of the deliverable from mg to multigram
• Exceptional purity

Large Scale Chemical Manufacturing

• Synthesis on Äkta^TM OP-100 and OP-400 synthesizer platforms
• Oligonucleotide synthesis up to 30mmol and more per synthesis run
• Manufacturing of:
  • Drug substance for GLP-Tox studies
  • Reference standards
  • Process related impurity markers
  • Oligonucleotides with 5’-Triphosphate and 5’-Diphosphate 
  • Process research to identify and optimise the synthesis and downstream processing parameters
  • Tech transfer thereof to support process development and GMP manufacturing

Organic synthesis lab 

• Synthesis in mg to multigram scale
  • Small molecules
  • Ligands for conjugation to nucleic acids
• Lipids for lipid nanoparticles (LNPs)  
  • Varied lipids synthesized: cationic, PEG, phospholipids etc.
  • For LNP formulation of oligonucleotides
  • Set of proprietary lipids available 
• Nanoparticle formulation for Functional Delivery