Development of an Integrated Microfluidic Platform for the Identification of Therapeutic Peptides for Unmet Medical Needs

制药工业已经认识到细胞渗透性肽对治疗目前无法治疗的疾病的重要性。事实上，肽可以与其他类型的分子不能的靶点相互作用，例如蛋白质-蛋白质相互作用，这在许多疾病的产生和进展中起着至关重要的作用。然而，肽也具有阻碍其用作药物的主要限制。其中之一是它们不能有效地与细胞内靶标相互作用，从而留下许多未满足的医疗需求。我们建议开发一个集成平台来生成和筛选肽库，以快速且具有成本效益地识别针对那些未开发的细胞内靶点的新药。在拟议研究的第一阶段，我们将集中精力建立这样一个平台，在第二阶段，我们将使用与癌症和囊性纤维化相关的两种不同的细胞内靶点对其进行验证。该项目的成功结果将导致药物发现领域的重大进展，因为目前的肽技术只能进入细胞外靶点，而忽略了75%位于细胞内的靶点。因此，我们的技术有可能为目前无法治愈的疾病或治疗选择有限的疾病提供改变患者生活的药物。

Pharmaceutical industries have recognised the importance of cell-permeable peptides to cure currently untreatable diseases. In fact, peptides can interact with targets that other type of molecules cannot, such as protein-protein interactions which play crucial roles in the generation and progression of many diseases. However, peptides also have major limitations that hamper their use as drugs. Among these is their inability to efficiently interact with intracellular targets leaving many unmet medical needs. We propose to develop an integrated platform to generate and screen libraries of peptides to rapidly and cost-effectively identify new drugs for those untapped intracellular targets. In the first phase of the proposed research, we will focus our efforts on building such a platform, and in the second phase we will validate it using two different intracellular targets with relevance in cancer and cystic fibrosis. A successful outcome to this project will result in a significant advance in the drug-discovery field as current peptide technologies can only access extracellular targets, ignoring those 75% located intracellularly. Therefore, our technology has the potential to provide patients with life-changing medicines for currently untreatable diseases or for diseases with limited therapeutic options available.