Ex vivo venous gene delivery by pulsed electric-fields

Information

  • Research Project
  • 6833413
  • ApplicationId
    6833413
  • Core Project Number
    R43HL075933
  • Full Project Number
    1R43HL075933-01A1
  • Serial Number
    75933
  • FOA Number
  • Sub Project Id
  • Project Start Date
    9/1/2004 - 19 years ago
  • Project End Date
    2/28/2006 - 18 years ago
  • Program Officer Name
    CHEUNG, GEOFFREY P.
  • Budget Start Date
    9/1/2004 - 19 years ago
  • Budget End Date
    2/28/2006 - 18 years ago
  • Fiscal Year
    2004
  • Support Year
    1
  • Suffix
    A1
  • Award Notice Date
    8/24/2004 - 19 years ago
Organizations

Ex vivo venous gene delivery by pulsed electric-fields

[unreadable] DESCRIPTION (provided by applicant): [unreadable] The long-term objective of this project is to make gene therapy based prevention of coronary and peripheral vascular graft-induced occlusion and restenosis feasible by developing a safe, effective and economical DNA delivery method based on electroporation. Electroporation employs electric field pulses to make cell membranes permeable for DNA, resulting in a 100-1000 fold increase of intracellular DNA delivery as compared to the "naked DNA" method. The proposed project involves designing and testing suitable electrodes and optimizing electroporation parameters in ex vivo organ culture, aimed eventually at applications for vein grafts in clinical settings. The specific aims of this project are: (1) to evaluate the efficiency of pulsed electric fields for ex vivo DNA transfer into cells of rat inferior vena cava and porcine saphenous vein, respectively. (2) to evaluate vasospastic & vasorelaxation effects of pulsed electric fields and (3) to design, develop and test electrodes based on experimental observations and theoretical computational modeling of electric fields. This investigational effort may provide a critical advancement for the delivery of therapeutic genes to the interstitial spaces and to the cyotosol with high efficiency and few side effects at a reasonable cost, superior to methods that have been tried in the past. The commercial product will be an innovative electroporation device and method for the efficient local delivery of therapeutic genes or compounds to enhance the success rate of vascular grafting for the prevention of vessel graft dysfunctions. Reducing the incidence of graft failure will save or prolong patients' lives and prevent the necessity of re-treatments which deplete scarce human as well as financial healthcare resources. The project goal will be to "condition" vein-graft ex vivo via gene transfer prior to its interpositioning with the target artery. In clinical settings the ex vivo treatment approach can be easily incorporated into the usual graft surgical procedure. It only requires the treatment of the graft before implantation. [unreadable] [unreadable] [unreadable]

IC Name
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
  • Activity
    R43
  • Administering IC
    HL
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    102865
  • Sub Project Total Cost
  • ARRA Funded
  • CFDA Code
    837
  • Ed Inst. Type
  • Funding ICs
    NHLBI:102865\
  • Funding Mechanism
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    GENETRONICS, INC.
  • Organization Department
  • Organization DUNS
    122735749
  • Organization City
    SAN DIEGO
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    921211318
  • Organization District
    UNITED STATES