Decoration and Dimerization of Chimeric Proteins Mediated by Coiled-Coil Interactions

制药行业是加拿大最赚钱的制造业之一，其实力依赖于持续创新，其战略发展的核心是配方。虽然纳米药物（例如药物抗体结合物和复杂的蛋白质组装体）是最新和最有前途的一代治疗药物，但业界仍在努力有效地设计和生产它们。Forbius是一家专注于开发治疗罕见疾病的新型生物治疗药物的加拿大公司，是这项合作研究和开发资助申请的工业合作伙伴。通过这个项目，蒙特利尔理工大学的研究人员和Forbius的研发团队之间的合作被提议，以设计Forbius的下一代疗法。拟议研究的核心是蒙特利尔理工学院的团队集中开发的一种多功能肽基缀合平台，该平台将用于设计1）药物与抗体缀合的新方法，2）作为潜在抑制剂进行测试的蛋白质的非天然二聚体，和3）一系列使能技术，有利于在项目背景下生产的肽和蛋白质的生产和纯化。该项目将涉及3个HQP-两名博士后研究员和一名博士生将在多学科环境中接受培训，并接触加拿大小型制药公司面临的工业挑战。随着2种药物进入临床试验阶段，Forbius正在迅速扩大其研发活动并积极招募。此外，仅在加拿大，就有20多家当地小型生物技术公司目前正在设计类似的产品。除了跨国制药公司的加拿大分公司外，他们都是本项目期间培训的HQP的潜在雇主。事实上，目前生物制造业对HQP的需求很高;这是维持这些公司在加拿大增长的项目的一个重要成果。

The pharmaceutical industry is one of the most profitable Canadian manufacturing sector and its strength relies on continuous innovation, with formulation at the core of its strategic development. While nano-medicine (e.g. drug-antibody conjugates and intricate assemblies of proteins) are the latest and most-promising generation of therapeutics, the industry still struggles to design and produce them efficiently.Forbius, a Canadian company focusing on the development of novel biotherapeutics to treat rare diseases, is the industrial partner of this Collaborative Research and Development Grant application. Through this project, a collaboration between researchers at Polytechnique Montréal, Université de Montréal and the R&D team at Forbius is proposed in order to design Forbius' next-generation therapeutics. At the heart of the proposed research is a versatile peptide-based conjugation platform intensively exploited by the team at Polytechnique Montreal, that will be applied to engineer 1) novel approaches for the conjugation of drugs to antibodies, 2) unnatural dimers of proteins to be tested as potential inhibitors, and 3) a portfolio of enabling technologies to favor the production and the purification of the peptides and proteins being produced in the context of the project.The project will involve 3 HQPs - two post-doctoral fellows and one PhD student - that will be trained in a multidisciplinary environment and exposed to the industrial challenges faced by small Canadian pharmaceutical companies. With 2 drugs in clinical trials phase, Forbius is now rapidly expanding its R&D activities and actively recruiting. Furthermore, within Canada only, more than twenty local small biotech companies are currently designing similar products. They all are, in addition to the Canadian branches of the multinational pharmaceutical companies, potential employers of the HQP trained during this project. Indeed, HQPs are currently in high demand in the biomanufacturing sector; this represents a significant outcome of the project to sustain the growth of these companies in Canada.