In this application, we propose a comprehensive National Gene Vector Repository (NGVB) which meets all the goals stated in RFA-RR-07-002.
The Specific Aims of the NGVB are:
Specific Aim 1. Develop and Oversee a Repository of Gene Therapy Reagents. The NGVB will gather a wide variety of gene therapy reagents that will be made available to academic investigators for preclinical investigation.
Specific Aim 2. Archive Samples Collected in the Performance of Clinical Trials or Pharmacology/Toxicology Studies. The NGVB will seek to provide a safe and secure storage site for biospecimens that must be collected to maintain compliance with FDA or other regulatory agencies.
Specific Aim 3. Expansion of a Pharmacology/Toxicology Database. Indiana University has maintained a web-based Pharmacology/Toxicology Database that allows investigators to search for studies that are relevant to their area of research. The unique resource will become the model for NGVB database and allow investigators to view the design of studies already on file with the FDA.
Specific Aim 4. Serve as a Coordinating Center. The NGVB Coordinating Center will facilitate the activities within Specific Aims 1-3. In addition, it will (1) organize an External Advisory Boards;(2) develop a Policy and Procedure Manual that defines the activities of the NGVB;(3) conduct outreach activities;(4) provide a """"""""help-desk"""""""" function for investigators seeking gene therapy reagents;(5) host a new and unique bioinformatics tool that aids in vector insertion site analysis, SeqMap.
Specific Aim 5. Research on Insertional Mutagenesis. To address the research requirements of the RFA, we will build on our ongoing work in a murine gene therapy model and will compare the lentiviral vector insertion pattern with our existing database of retroviral insertions. If this system proves to be a predictor of clonal selection, it can be used to validate other, ideally in vitro, models of risk.