Large Scale Oligonucleotide Production

In the past decades, synthetic oligonucleotides have been explored for therapeutic purposes and seven oligonucleotide drugs have been successfully approved by FDA. The increase in demand for a large quantity of oligonucleotide material for therapeutic applications has led to more cost-effective manufacturing technologies. Creative Biolabs has improved the quality of synthetic oligonucleotides by using raw materials with the highest possible purity. At the same time, yields have been increased significantly by continuous development and optimization of oligonucleotide manufacturing processes. We offer multi-gram large scale oligonucleotide synthesis with competitive price, and fast turnaround time.

Large Scale DNA and RNA Oligonucleotide Production Services

  • Synthesis: Solid-phase synthesis has been employed for the manufacture of oligonucleotides from micrograms for research use. During solid-phase synthesis, phosphoramidite monomers are added sequentially onto a solid support to generate the desired full-length oligonucleotide. Each cycle of base addition consists of four chemical reactions, detritylation, coupling, oxidation/thiolation, and capping.
  • Cleavage and Deprotection (C&D): Oligonucleotide deprotection involves three steps: removal of a cyanoethyl protecting group from the phosphate backbone, cleavage of the oligonucleotide chain from the support, and base deprotection. This process is generally carried out in batch mode where the entirety of the solid support is incubated with C&D reagents.
  • Purification: The purification of oligonucleotide crude solutions is generally achieved by chromatographic methods. Taking advantage of the internucleotide phosphodiester (PO) and phosphorothioate (PS) linkage, anion exchanged and ion-paired reversed-phase (IP-RP) chromatographic purifications on HPLC equipment are widely used for the purification of the therapeutic oligonucleotide.
  • Desalting and Concentration: The most widely accepted choice for therapeutic oligonucleotide isolation at manufacturing scales is the use of tangential flow filtration (TFF). This approach employs an appropriately sized filter membrane and uses a pump to circulate the sample through the TFF set-up making the process more efficient.
  • Lyophilization: This step is performed using a freezer dryer, which is a machine consisting of a sample chamber, a condenser and a vacuum pump. The oligonucleotide is frozen and lyophilized to obtain the final product in powder form via sublimation.

Oligonucleotide production process steps. Figure 1. Oligonucleotide production process steps.

Advantages

  • Midscale to large scale synthesis per lot
  • Flexible ordering methods
  • PS, PO or PO/PS backbone
  • Wide variety of oligonucleotide modifications
  • Custom analytic method development
  • Product compliance verification (HPLC, PAGE, MALDI-TOF or LC-MS/MS)

With over years of experience in oligonucleotide synthesis services, Creative Biolabs provides large-scale oligonucleotide production for therapeutic projects worldwide. Using various synthesis technologies, we manufacture highly complex DNA and RNA oligonucleotides, which are produced for high-throughput or commercial applications in multi-gram quantities of highly purified antisense oligos, siRNAs, and miRNA. All large scale oligonucleotides are manufactured under strict quality management standards. If you are interested in our services, please contact us for more details.

For research use only. Not intended for any clinical use.