Technologies for Liquid-Phase Synthesis of Oligonucleotides

Request Number REQ8341979
Due Date April 19, 2017
Author Seh-Rin Sung
Request for Proposal Details
RFP Title
Technologies for Liquid-Phase Synthesis of Oligonucleotides
RFP Description

NineSigma, representing a global pharmaceutical company, seeks technologies for liquid-phase synthesis of oligonucleotides, such as siRNA and antisense oligonucleotides.


The client aims to improve production cost efficiency for nucleic acid drugs, which are a next-generation modality of drugs, and expect that liquid-phase synthesis technologies are a promising approach to achieving the goal. 


Solid-phase synthesis methods are currently being used to synthesize nucleic acid drugs (likewise peptide drugs). However, their manufacturing cost is so high that their applicability is restricted to critical illnesses for which high drug prices are accepted. In order to expand the scope of nucleic acid drug applicability, it is necessary to use a liquid-phase synthesis method, which is anticipated to be a highly cost-effective synthesis method.


The client therefore initiated this request for information to find a partner organization possessing a liquid-phase synthesis technology, to take a first step toward expediting research and development. 



Key Success Criteria

A wide range of technologies are anticipated from companies or academic institutions possessing the following liquid-phase (solution-phase) synthesis technologies. 


Anticipated liquid-phase synthesis technologies:

Technologies for synthesizing in a fully liquid phase

  • Technologies capable of synthesizing oligonucleotides in a liquid (solution) phase, without loading nucleosides on a solid phase carrier (support) or the like (including solvent-soluble carriers).
    • Technologies capable of synthesizing oligonucleotides through elongation not only by monomer units, but also elongation by short-chain oligomers, such as dimers and trimers. (i.e. “block synthesis”)
    • It is desirable that manufacturing lead time can be decreasing through the avoiding purification processes, the shortening of processes, or the using concise processes.
  • Liquid-phase synthesis technologies using phase switching
    • Oligonucleotide synthesis technologies using a soluble carrier that disperses/ precipitates according to the solvent used.
    • In addition to the above, technologies using ionic liquids, fluorous solvents, etc. are also acceptable.


Anticipated component technologies

Proposals for technologies which fulfill any one of the following are anticipated.

  • Technologies with efficient phosphodiester bond formation reactions
    • Should be more cost-effective than the conventional amidite method
    • Superior reactivity
    • Intermediate shows good properties, such as stability. 
  • Technologies with phase switching soluble carriers capable of imparting favorable physical properties to oligonucleotides 
    • Capable of imparting solubility and the like needed for oligonucleotide synthesis reactions
    • High precision analysis is feasible
    • Efficient purification is feasible
    • Feasible in “block synthesis”.

Without restricting proposals to the above, proposals for any innovative technology which greatly reduces the costs of oligonucleotide synthesis are welcome.


Targeted types of nucleic acids

  • RNA
  • DNA
  • Modified nucleotides such as 2’ -OMe, 2’ -F, LNA (Locked Nucleic Acid), BNA (Bridged Nucleic Acid)
  • Phosphorothioate linkages


Approaches not of interest

The following approaches are not of interest:

  • Solid-phase synthesis technologies



Preferred Collaboration types
  • To Be Negotiated
Items to be submitted

Notes for Your Proposal Submission

Please note the following points when submitting information:

  • Enter your organization’s information into the template for submitting information at the bottome of this page, and send it to Ogata (
  • Please fill out the following information in the Response template (No confidential information is required at this stage) :
    • Overview of the proposed technology (principle, characteristics, intended application, etc.)
    • Uniqueness of the proposed technology
    • Current performance
      • Targeted monomers
      • Cost reducing capabilities (if any)
    • Future research and development plans and production system plans based on GMP (including partnerships, etc.)
    • Information about the organization (past achievements, etc.)
  • In the event that it is difficult to fill out the above Response template, please send any materials (papers, presentation materials, etc.) that will enable the overview of the synthesis technology and the current state of performance to be ascertained.


Process After Your Proposal Submission

NineSigma will introduce the technical information it receives to the client company. If the client company takes an interest in any of the technical information, it will contact the corresponding provider of the information directly. If the technology is finally adopted, it will open up opportunities for joint development, contract development, technology licensing.

Area of Interest
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