Development of a Gene and Oligonucleotide Delivery System

Information

  • Research Project
  • 8981573
  • ApplicationId
    8981573
  • Core Project Number
    R41TR001338
  • Full Project Number
    1R41TR001338-01
  • Serial Number
    001338
  • FOA Number
    PA-14-308
  • Sub Project Id
  • Project Start Date
    9/1/2015 - 10 years ago
  • Project End Date
    8/31/2016 - 9 years ago
  • Program Officer Name
    BROOKS, PJ
  • Budget Start Date
    9/1/2015 - 10 years ago
  • Budget End Date
    8/31/2016 - 9 years ago
  • Fiscal Year
    2015
  • Support Year
    01
  • Suffix
  • Award Notice Date
    8/20/2015 - 10 years ago
Organizations

Development of a Gene and Oligonucleotide Delivery System

? DESCRIPTION (provided by applicant): The knockdown of targeted genes by anti-sense oligonucleotides (ODNS) and genetic medicines (collectively, G-MEDS) holds promise for a variety of therapies. The delivery of effective quantities of ODNS to specific cells, however, has proved to be challenging. We propose here a novel approach to ODN delivery that involves enveloped virus-like-particles (EVLPs). These delivery agents are prepared by the in vitro self- assembly of pure G-MEDS and pure viral capsid protein (CP) into virus-like nanoparticles particles (VLPs). The capsid protects the contents yet, as we have demonstrated, is capable of giving up its contents in the cytoplasm of mammalian cells. The particles, which are highly mono-disperse, are then enveloped by lipid bilayers that can suppress the immunogenicity of the VLPs and are capable of being functionalized for targeting and uptake by mammalian cells of interest. In preliminary experiments, we have demonstrated our ability to prepare EVLPs using the CP of the cowpea chlorotic mottle virus and a model antisense ODN for vascular endothelial growth factor (VEGF), a protein over-expressed in many cancer cells to stimulate angiogenesis a facilitate tumor survival under low- oxygen conditions. We propose to optimize the assembly and to functionalize the lipid bilayers with epidermal growth factor (EGF), which binds the EGF receptor that is over-expressed on cancer cells, especially those of breast cancer. The effectiveness of the EVLP will be demonstrated by assaying the reduction in the secretion of VEGF in cultured breast cancer cells.

IC Name
NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
  • Activity
    R41
  • Administering IC
    TR
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    322946
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    350
  • Ed Inst. Type
  • Funding ICs
    NCATS:322946\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    MOLECULAR EXPRESS, INC.
  • Organization Department
  • Organization DUNS
    058878682
  • Organization City
    RANCHO DOMINGUEZ
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    902205610
  • Organization District
    UNITED STATES