High throughput cell-based functional screening platform for peptide drug discovery

用于肽药物发现的高通量细胞功能筛选平台

• 批准号: 10029273
• 金额: $ 42.17万
• 依托单位: ORBIT DISCOVERY LTD
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=10029273
• 关键词: throughput; cell; based; functional; screening

Orbit Discovery is a UK-based SME pioneering the discovery and development of novel peptide therapeutics.Peptides represent a unique class of pharmaceutical compound, having incredibly high chemical diversity, molecularly poised between small molecules and proteins, yet biochemically and therapeutically distinct from both. Peptide therapeutics typically combine the specificity and efficacy of large biological molecules with the smaller dose-size, simpler delivery routes and lower manufacturing costs of small molecule therapeutics.The growing realisation in drug discovery is the need to screen targets (including a range of biological entities which may include proteins, genes and RNA) in as close to their natural contexts as possible. Biopharmaceutical companies developing novel drug therapies have a **currently unmet yet critical need** to identify drugs that both **bind to the target** and **induce a functional response**. Previously, the primary source of clinical trial failure has been, and remains, an inability to demonstrate efficacy; mostly due to screening of targets out of their native physiological context. Traditional screening methodologies typically make use of recombinant forms of protein targets isolated in solution. Orbit proposes to screen targets directly on cells to identify peptides that not only bind but also elicit a functional response. Orbit has previously demonstrated a proof-of-concept for its cell-based peptide library screening method which has the potential to **address a significant need** for its target customers (bio/pharmaceutical firms developing peptide therapeutics), providing a radical step-change in the speed of discovery of novel functional peptides.In this project, Orbit will develop a crucial part of the platform implementing droplet-based microfluidics for cell-functional screening. This game-changing droplet-based screen will enable high-throughput screening against cell-based drug targets for the discovery of **functional** peptide drug candidates. This will significantly reduce screening cost, labour, and time.The project will address difficult to access drug targets in biologically relevant contexts; will cause disruption to the drug discovery and development markets as well as the peptide therapeutics market, positioning Orbit as the leading peptide drug discovery company globally.

Orbit Discovery是一家总部位于英国的中小企业，致力于发现和开发新型肽疗法。多肽代表了一类独特的药物化合物，具有令人难以置信的高度化学多样性，分子平衡在小分子和蛋白质之间，但在生物化学和治疗上却与两者不同。肽治疗通常结合了大生物分子的特异性和有效性，以及小分子治疗的较小剂量、更简单的递送途径和更低的制造成本。在药物发现中，越来越多的人认识到需要在尽可能接近其自然环境的情况下筛选靶标（包括一系列生物实体，可能包括蛋白质、基因和RNA）。开发新药物疗法的生物制药公司目前有一个尚未满足的关键需求，即确定既能与靶标结合又能诱导功能性反应的药物。以前，临床试验失败的主要原因一直是，而且仍然是无法证明疗效；这主要是由于对目标的筛选脱离了它们原有的生理环境。传统的筛选方法通常使用在溶液中分离的重组形式的蛋白靶标。Orbit建议直接在细胞上筛选目标，以识别不仅结合而且引起功能反应的肽。Orbit先前已经展示了其基于细胞的肽库筛选方法的概念验证，该方法有可能满足其目标客户（开发肽疗法的生物/制药公司）的重大需求，为发现新型功能肽的速度提供了根本性的变化。在这个项目中，Orbit将开发平台的关键部分，实现用于细胞功能筛选的基于液滴的微流体。这种改变游戏规则的基于液滴的筛选将使基于细胞的药物靶点的高通量筛选成为可能，从而发现功能性肽候选药物。这将大大减少筛选成本、人工和时间。该项目将解决在生物学相关情况下难以获得药物靶点的问题；将对药物发现和开发市场以及多肽治疗市场造成破坏，使Orbit成为全球领先的多肽药物发现公司。