(This application was written in response to the NIH Announcement for the Availability of Recovery Act Funds for Competitive Revision Applications (NOT-OD-09-058). The experiments outlined in this application were designed to expand the scope of the specific aims, research design, and methods of the parent grant (RO1 EB007357) entitled """"""""Image-guided Hydrodynamic Gene Delivery"""""""". The objective of the parent grant is to develop an image-guided hydrodynamic gene delivery system for site-specific gene delivery to the liver. Since the start of the project last year, we have established the procedure using pigs as an animal model and demonstrated that the image-guided hydrodynamic gene delivery is highly effective and safe for liver gene delivery. In this competitive revision application we propose to expand the study by including the non-human primate as an additional animal model for further development. We plan to systematically assess the effectiveness of the image-guided hydrodynamic gene delivery in baboons in order to establish the hydrodynamic parameters that can be used for development of a computer program for gene delivery in humans.
The specific aims are: (1) To study the effect of selected injection pressures and volumes of DNA solution on gene delivery efficiency to baboon liver, and (2) to assess the persistency of transgene expression and the long-term effect of hydrodynamic procedure on the transfected animals. In compliance to Acceleration of the Tempo of Scientific Research and/or Allow for Job Creation and Retention, We are going to hire two full time employees for the proposed study. In addition, the use of animals will also create job for those who are animal caring professionals. The reagents used in the proposed would also help in creating or retaining people who work in research reagent companies.
(Gene therapy has been studied as an alternative method for treatment of many different diseases, ranging from a single gene defect to complex conditions due to both genetic and environmental factors. However, its tremendous potential to provide highly specific, safe, and effective treatments can be realized only with development of safe and effective gene delivery system. Experiments outlined in this proposal are extension of our recent work in developing an image-guided, computer-controlled hydrodynamic gene delivery for human gene therapy. The goal of the proposed study is to validate the effectiveness and safety of the simplest gene delivery system for gene delivery to liver in non-human primates. Results obtained will provide guidance for preparation for clinical evaluation.
Showing the most recent 10 out of 30 publications
