Scalable AAV production in high density suspension HEK293SF-3F6 cell culture using Nanocin transfection

病毒载体是医学基因治疗革命的核心，并已显示出对患者的变革性好处。病毒的制造本质上是复杂的，其中一个关键挑战是将编码DNA的病毒引入到培养中生长的生产细胞中。这一高价值制造业领域令人振奋，具有重要的战略意义，目前正在随着制造商开发创新工艺而发生变化。该项目加入了快速发展的英国中小企业和世界领先的生物工艺开发中心。这一合作伙伴关系补充了优势，并共同推动开发腺相关病毒(AAV)生产的改进解决方案，该解决方案可被视为基因治疗领域的一匹“工作马”。其目标是开发更高效、更便宜、对供应挑战有弹性、并与客户现有设施和长期制造计划兼容的灵活工艺。该项目将使用业界领先的PEI产品(Polyplus；欧盟/美国)作为基准，我们的目标是利用Nanocin的优势特性，开发与临床应用兼容的可扩展格式的生产工艺。Nanocin的低毒特性使重复转基因(DNA传递)成为可能，这种进步整合到商业生物反应器中可以带来制造效率的逐步变化和成本的降低。好处将流向Tecrea和英国高价值的先进药品制造行业，无论是地区(就潜在集群而言)还是全国。NRC将受益于提高其生物处理能力，最重要的是提高基因疗法的质量和成本，使其能够在加拿大境内对公众健康产生重大好处。

Viral vectors are central to the gene therapy revolution of medicine and have demonstrated transformative patient benefits. The manufacturing of viruses is inherently complex, where a key challenge is the introduction of virus encoding DNA into producer cells grown in culture. This area of high-value manufacturing is exciting, strategically important, and currently transforming as manufacturers develop innovative processes. This project joins a rapidly growing UK SME with a world-leading bioprocess development centre. This partnership complements strengths and a joint motivation to develop an improved solution for adeno- associated virus (AAV) production, which can be considered to be a "work horse" within the gene therapy area. The aim is to develop flexible processes that are more efficient, less expensive, resilient to supply challenges, and compatible with customers' existing facilities and long-term manufacturing plans. We will reach our goals by combining and building on previous work in the area-field.The project will use the industry-leading PEI product (Polyplus;EU/US), as a benchmark, where we aim to exploit the advantageous properties of Nanocin and develop production processes in a scalable format that is compatible with clinical applications. The low toxicity properties of Nanocin enable repeat transfection (DNA delivery), and such advances, integrated into commercial bioreactors can provide step changes in manufacturing efficiencies and cost reductions.Benefits will flow to Tecrea and the UK high-value advanced medicines manufacturing industry, both regionally (in terms of potential clustering) and nationally. NRC will benefit by advancing its bioprocessing capacities and most importantly improve the quality and cost of gene therapies to the extent that they can have a substantial public health benefit within Canada.