The National Gene Vector Biorepository (NGVB) at Indiana University has serves as a national resource for the gene therapy community since 2008. We propose to continue this resource and propose the following Specific Aims:
Specific Aim 1. Reagent Repository. The NGVB will expand current efforts in reagent sharing through a web- based catalogue of gene therapy reagents, including plasmids, cell lines, and vectors. In the new funding period, a special focus will be on obtained novel reagents in the area of non-viral gene therapy, IPS cell generation, and transposon technology.
Specific Aim 2. Preclinical Assistance: Meeting the Challenges of FDA Preclinical Pharmacology and Toxicology Requirements. The NGVB will provide archiving services for Good Laboratory Practice (GLP) samples and a web-based database of completed gene therapy biodistribution and toxicity studies (Pharm/Tox database). New initiatives will include an expansion of the database to cover key non-GLP studies and the establishment of the In Vitro Immortalization Assay.
Specific Aim 3. Clinical Trial Support of Gene Therapy Studies. The NGVB will continue to provide archiving, RCV testing, and LAM-PCR for insertion site analysis in support of gene therapy clinical trials. The NGVB will also expand the capabilities of the SeqMap bioinformatics tool that assists in the analysis of sequence data generated from Sanger or high-throughput sequencing techniques. Finally, the NGVB will prepare for the bioinformatics challenges of short-read sequencing by developing SeqMap 3.0.
Specific Aim 4. Research and Develop a Qualified Assay for Insertion Site Analysis. We propose to develop a standard set of reagents and protocols that will provide important internal controls for investigators conducting these studies. We will also develop a standardize assay designed specifically to meet the FDA requirements and improve the clinical relevance of assay output.
Gene therapy continues to hold promise for many patients with life-threatening and debilitating diseases. As academic institutions remain the focal point of gene therapy research, a national effort that fosters access to novel reagents, promotes data sharing, and provides services that help investigators meet the unique FDA regulatory requirements surrounding gene therapy will be key to accelerating new therapies.
|Shaw, A M; Joseph, G L; Jasti, A C et al. (2017) Differences in vector-genome processing and illegitimate integration of non-integrating lentiviral vectors. Gene Ther 24:12-20|
|Boeke, Aaron; Doumas, Patrick; Reeves, Lilith et al. (2013) Vector production in an academic environment: a tool to assess production costs. Hum Gene Ther Methods 24:49-57|
|Du, Lily M; Nurden, Paquita; Nurden, Alan T et al. (2013) Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A. Nat Commun 4:2773|
|Cornetta, Kenneth; Brown, Candy Gunther (2013) Balancing personalized medicine and personalized care. Acad Med 88:309-13|
|Cornetta, Kenneth; Tessanne, Kimberly; Long, Charles et al. (2013) Transgenic sheep generated by lentiviral vectors: safety and integration analysis of surrogates and their offspring. Transgenic Res 22:737-45|
|Tremblay, Jacques P; Xiao, Xiao; Aartsma-Rus, Annemieke et al. (2013) Translating the genomics revolution: the need for an international gene therapy consortium for monogenic diseases. Mol Ther 21:266-8|
|O'Reilly, Marina; Kohn, Donald B; Bartlett, Jeffrey et al. (2013) Gene therapy for rare diseases: summary of a National Institutes of Health workshop, September 13, 2012. Hum Gene Ther 24:355-62|
|Aloia, A L; Duffy, L; Pak, V et al. (2013) A reporter system for replication-competent gammaretroviruses: the inGluc-MLV-DERSE assay. Gene Ther 20:169-76|
|Bear, Adham S; Morgan, Richard A; Cornetta, Kenneth et al. (2012) Replication-competent retroviruses in gene-modified T cells used in clinical trials: is it time to revise the testing requirements? Mol Ther 20:246-9|
|Cornetta, Kenneth; Yao, Jing; Jasti, Aparna et al. (2011) Replication-competent lentivirus analysis of clinical grade vector products. Mol Ther 19:557-66|