Novel Cationic Lipids for the Encapsulation of Nucleic Acids as Therapeutic Nanoparticles

Request Number N635071
Need details

Pfizer seeks partners who can identify and/or synthesize novel ionizable cationic lipids with a high therapeutic index and low toxicity profiles. The ionizable cationic lipids must be suitable for use in self-assembly and encapsulation of therapeutic mRNA within lipid-based nanoparticles. The nanoparticles must enable delivery and release of the mRNA in cells such as hepatocytes in liver.


Such diseases include, but are not limited to, Type 2 diabetes (particularly young and low BMI diabetes) and related complications, hepatocellular carcinoma (HCC), gastric cancer and COPD.


Pfizer seeks to provide seed funding to a limited number of Asia’s leading academic and biotechnology groups to create new partnerships that address this need.  Seed funding from US$50,000 to US$1,000,000 per year may be provided to support research collaborations that can help transition these opportunities from the academic environment into new start-up companies.


Key Success Criteria:

Successful proposals should address the following:

    1. Synthesis and in vivo testing of small libraries of ionizable cationic lipids
    2. Lipids must possess properties of strong self-assembly with mRNA, antisense oligonucleotides or siRNA
    3. The resulting nanoparticles must exhibit efficient endosomal disruption with evidence of release of content after delivery in cells such as hepatocytes in liver
    4. As a guide, publications relating to the lipidoid C12-200 (Love, K.T. et al., 2010 PNAS 107, pp1864-69) and the amino lipids Dlin-KC-2DMA and DLin-MC3-DMA (Jayaraman , M., 2012 Angew. Chem. Int. Ed. 51, 8529-33) serve as minimum standards of ionizable cationic lipids with high therapeutic index and low toxicity profiles.  Evaluation of the chemical stability of the formulated lipids in neutral aqueous buffers is essential.



is working with nanoparticles for the delivery of mRNA, siRNA and antisense oligonucleotides as approaches to biologics therapy. Cationic lipids enable the self-assembly of nucleic acids as nanoparticles that form in discrete sizes. The polyanionic nature and large molecular weight of siRNA and mRNA require transmembrane delivery technologies to facilitate uptake and release of these nucleic acids to the cell cytoplasm where they effect therapeutic changes in cells.


Lipid-based nanoparticles are achieving validation as vehicles for the delivery of therapeutic nucleic acids such as siRNA and mRNA to tissues such as liver (Rehman, Z., et al., 2013 Journal Controlled Release, 166, pp 46-56). However not all cationic lipids are created equal. Early formulations relied on permanently charged amine moieties for the self-assembly of nanoparticles, but their delivery of siRNA to liver resulted in poor gene knock-down, which may have been caused by poor release of content after uptake in hepatic endosomes. Newer generations of ionizable amino lipids have received attention for their merits in the self-assembly of nanoparticles along with their favorable release of active pharmaceutical ingredient once they have been taken up by target tissues. The ability of these lipids to restore a maximum positive charge in the acidified lumen of endosomes is believed to promote membrane disruption and to facilitate release. A role of ApoE-mediated endocytosis of nanoparticles by hepatocytes is postulated for some of the cationic lipids that present a minimal charge at pH 7.4 in plasma (Jayaraman et al., Angew 2012, ibid). However, a different class of cationic lipids, called lipidoids, that do not bind ApoE achieve equally high therapeutic indices for siRNA delivery to hepatocytes (Akinc, A., et al., 2008 Nature Biotechnology 26, pp 561-69). Although these newer ionizable cationic lipids are being evaluated in clinical trials and they hold promise for the delivery of nucleic acid therapies, the options and availability of these newer lipids are limited.


Pfizer is pursuing the delivery of nucleic acids for, among other things, the expression of proteins in vivo. When the multiple pathways of internalization that are used by cells are combined with the range of variations in the mechanisms for intracellular trafficking, it becomes evident that there is ample room, as well as need, for the development of novel cationic lipids to facilitate the investigation and development of refinements in nanoparticle delivery of nucleic acids.


Possible Approaches:

Expertise in developing novel cationic lipids, together with evidence of in vivo efficacy for the delivery of mRNA, antisense oligonucleotides or siRNA


Approaches Not of Interest:

Approaches that do not use cationic lipids, e.g., polymers such as polyethyenimine, are not of interest at this time.


Legal Requirements:

The partner organization must hold full rights to license (or sublicense) the cationic lipids or encapsulation methods.


How to Respond:

We are looking for a concise abstract/executive summary.  The proposal should include a completed required Response Template to briefly describe the technical approach and provide information on technology performance, background and description of the responding team and their related experience.


By submitting a response you represent that the response does not contain and will not be deemed to contain any confidential information of any kind whatsoever. All Personal Information disclosed to Pfizer within a response will be utilized in accord with principles and polices as described at By submitting a response, you also acknowledge and confirm that you have consulted with your Technology Transfer Office, Business Development Office or any other required group and that you have their approval to submit the response. By submitting a response, you acknowledge that the Need's sponsoring organization, in its sole discretion, may select or reject a response or any portion thereof.


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Migrated from previous NineSights Community Site
Key Success Criteria
Migrated from previous NineSights Community Site
Preferred Collaboration types
  • To Be Negotiated
Point of Contact
Jonathan Tzeng
Area of Interest
  • Chemical Manufacturing
  • Energy & Power Production
  • Family & Consumer Products & Services
  • Financial Services
  • Food & Beverage
  • Manufacturing & Fabrication
  • Medical Products & Services
  • Other
Due Date
May 2, 2014
Award Amount
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