CORE--ISLET TARGETING

Duke University, Durham NC

Investigators

Linked publications & trials

Abstract

The purpose of this core will be to provide novel technologies for targeting of molecular cargo to[unreadable] pancreatic islets, both in vitro and in living animals, to all three projects in this program. The two[unreadable] novel technologies resident in this core were developed under the auspices of the former Project 3 of[unreadable] this program in the previous five-year funding cycle. The first approach involves application of[unreadable] ultrasound microbubble destruction (UTMD) technology for highly efficient and specific gene delivery[unreadable] to pancreatic islet beta-cells of adult animals in vivo. The second approach evolved from studies in[unreadable] which we screened an M13 phage display library to identify peptides that bind specifically to[unreadable] pancreatic islet beta-cells, and subsequently demonstrated that the cognate phage targets islet beta-cells of[unreadable] adult animals in a selective fashion. We believe that these technologies will have different immediate[unreadable] applications to the three projects, so we propose to deploy these technologies in three activity centers:[unreadable] 1) At Duke, Dr. Hans Hohmeier and colleagues will work with Dr. Paul Grayburn to optimize the[unreadable] UTMD technology for delivery of genes to beta-cells of living Zucker Diabetic fatty rats, and will then[unreadable] perform studies aimed at reversing or preventing beta-cell failure of diabetes in these animals in close[unreadable] collaboration with Project 1; 2) At the Baylor Medical Center in Dallas, Dr. Grayburn and colleagues[unreadable] will collaborate closely with Project 3 to develop UTMD-based methods for delivery of targeted[unreadable] transcriptional activators to islet beta-cells, in both the in vitro and in vivo settings; 3) At UT Southwestern[unreadable] Medical Center in Dallas, Dr. Kathlynn Brown will optimize beta-cell targeting peptides for delivery of novel[unreadable] imaging agents to islets in both the in vitro and in vivo settings, in close collaboration with Project 2.[unreadable] We believe that the novel beta-cell targeting methodologies resident in Core B provide the PPG team with[unreadable] a remarkable opportunity for rapid translation of discoveries relating to beta-cell therapeutic genes[unreadable] (Project 1), novel imaging agents (Project 2), and targeted transcriptional activators (Project 3) to[unreadable] animal models of diabetes, and if proven and validated, to human diabetes therapy.