Developing the Caf1 polymer technology into a commercial propositionEP/T005963/1

制药业的发展经历了三次制造业革命。第一次出现在19世纪，人们能够化学合成以前只能从天然来源获得的药物（阿司匹林、奎宁）。接下来，在20世纪70年代，生物技术革命使胰岛素、凝血因子或抗体等蛋白质得以发展成为安全的广泛治疗方法。目前，我们正处于细胞治疗革命的中期，在体外培养人体细胞的能力正被用来创造基于细胞的治疗方法。更一般地说，人工细胞培养是一项广泛而迅速发展的技术，在医学、生物加工、作物科学、药物开发和临床研究中都有应用。近年来，细胞疗法的想法已经从单纯的可能性发展到白血病、中风、失明和关节炎等疾病的实际治疗。这不仅要求细胞能够在体外生长，还要求它们在重新植入患者体内之前能够进行繁殖和修饰。在许多情况下，人体的免疫系统将细胞疗法限制在自体形式，即从患者身上获得原始细胞，生长和/或修饰，然后重新引入。然而，用于治疗中风或遗传性失明等疾病的几种同种异体疗法也在开发中，其中一种商业细胞系用于治疗许多患者。许多工作依赖于干细胞的生长，干细胞是一种“原材料”，可以转化为广泛的医学应用组织类型。培养足够数量的干细胞以满足各种治疗的需要仍然是一个重大挑战。研究实验室中使用的细胞通常因其在塑料表面上快速和无限期生长的能力而被选择，但用于治疗的细胞需要类似生命的环境，并且以高度调节的方式生长。目前，细胞在表面上的培养主要分为两类；低成本，散装材料，例如塑料盘子，或高成本，小体积的生物基质，它们可以重现体内的条件，随着要求更高或更脆弱的细胞类型的使用，它们变得越来越重要。该项目旨在利用最近开发的专利工业工艺，以低成本制造具有先进细胞功能的工程蛋白聚合物，从而颠覆这一产品格局。通过弥合传统聚合物科学和蛋白质生物化学之间的差距，我们可以创造一系列基质来帮助许多下游应用的细胞生长。这个为期18个月的项目由细胞和基因治疗弹射器（Cell and Gene Therapy Catapult）支持，将首先开发一种用于快速发展的干细胞行业的先导产品。这是用我们的蛋白质聚合物在塑料表面涂上一层简单的涂层，在干细胞培养方面已经显示出明显的优势。独立验证将使我们能够着手其商业开发，以降低成本，提高整个细胞治疗部门的效率。然后，我们打算通过与该领域和工业界的领先研究小组合作，进一步证明其在肌肉、神经和软骨工作中的更广泛适用性。我们还将测试其在为细胞和组织培养重建更逼真的三维环境中的实用性。最后，通过利用我们最近的一项发展，将大型蛋白质模块包含在聚合物中，我们将创建一个基质，可以用在自然细胞外环境中发现的任何数量的细胞修饰分子来装饰。这提供了一个前所未有的机会，可以在“试管”中创建定制的复杂细胞生长环境，同时使用易于商业化的产品和新的知识产权，我们打算在项目结束时果断地向分拆公司或许可协议迈进。

Pharmaceuticals have developed via three manufacturing revolutions. The first arose in the 19th century from the ability to chemically synthesise drugs previously only obtainable from natural sources (aspirin, quinine). Next in the 1970's the biotechnology revolution enabled proteins such as insulin, clotting factors or antibodies to be developed into safe widespread treatments. Currently we are in the midst of the cell therapy revolution where the ability to grow human cells outside the body is being exploited to create cell based treatments.More generally, artificial cell culture is a widespread and rapidly expanding technology with applications in medicine, bioprocessing, crop science, drug development and clinical research. In recent years the idea of cell based therapies has moved from mere possibility to actual treatments for conditions such as leukaemia, stroke, blindness and arthritis. These require not only that cells can be grown outside the body but that they can be multiplied and modified before reintroduction into the patient. In many cases the body's immune system restricts cell therapies to autologous forms where the original cells are obtained from the patient, grown and or modified and then reintroduced. However several allogeneic treatments, where a commercial cell line is used to treat many patients, are also in development for conditions such as stroke or inherited blindness.Much work depends upon growing stem cells which are a "raw material" that can be transformed into a wide range of tissue types for medical applications. Growing sufficient numbers of stem cells to satisfy the needs of various treatments is still a significant challenge. Cells used in research laboratories are often selected for their ability to grow rapidly and indefinitely on plastic surfaces but cells for therapy need life like environments and grow in a highly regulated manner.Currently, cells are cultured on surfaces that largely fall into two groups; low cost, bulk materials, exemplified by plastic dishes, or high cost, low volume biological matrices which recreate the conditions found within the body and are increasingly important as more demanding or fragile cell types are used. This project seeks to use a recently developed and patented industrial process to overturn this product landscape by manufacturing engineered protein polymers with advanced cellular functions at low cost. By bridging the gap between traditional polymer science and protein biochemistry we can create a range of matrices to assist the growth of cells for many downstream applications. The 18 month project, supported by the Cell and Gene Therapy Catapult will start by developing one lead product for use in the rapidly expanding stem cell industry. This uses simple coating of plastic surfaces by our protein polymer and has already shown significant advantages over rival technologies in stem cell culture in our hands. Independent validation will enable us to embark on its commercial exploitation to reduce costs and increase efficiency of the whole cell therapy sector. We then intend to further demonstrate its wider applicability for work on muscle, nerve and cartilage by collaboration with leading research groups in the field and with industry. We will also test its usefulness in recreating even more realistic 3 dimensional environments for cell and tissue culture.Finally by exploiting a recent development by us to include large protein modules within the polymer we will create a matrix which can be decorated with any number of cell modifying molecules which are found in natural extracellular environment. This offers an unprecedented opportunity to create bespoke complex cell growth environments in the "test tube"Using both readily commercialisable products and the new intellectual property we intend to move decisively toward either spin out company or licensing agreement at the end of this project.