Development of platforms for beta cell-specific delivery and ligand discovery

患有1型糖尿病的患者必须经历负担沉重的、通常是终生的外源性胰岛素依赖。到目前为止，唯一可用的替代疗法是从身体捐赠者身上移植胰岛。然而，这样的程序带来了一些障碍，比如可用的捐赠者稀缺，以及患者自身免疫系统对移植细胞的排斥。而且，随着时间的推移，移植的胰岛往往会死亡。为了规避这些影响，我们和其他人已经确定了几个诱导β细胞增殖的治疗靶点。然而，实现这些靶点的治疗潜力需要靶向释放，因为这些靶点的治疗窗口很窄。我们建议应用化学生物学方法来开发体内β细胞中生物活性物质的靶向释放方法。 1

Patients suffering from type 1 diabetes must undergo burdensome, often lifelong, exogenous insulin dependence. Up to now, the only available replacement therapy is to transplant islets from cadaveric donors. However, such procedures present hurdles such as the scarcity of available donors and the rejection of transplanted cells by the patient’s own immune system. Also, over time, the transplanted islets tend to die. To circumvent these effects, we and other have identified several therapeutic targets to induce beta cell proliferation. However, the realization of the therapeutic potential of these targets requires targeted release as the therapeutic window of these targets is narrow. We propose to apply chemical biology approaches to develop methods for targeted release of bioactives in beta cells in vivo. 1