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，并已证明具有变革性的患者益处。病毒的制造本质上是复杂的，其中一个关键挑战是将病毒编码DNA引入培养物中生长的生产细胞中。这一高价值制造领域令人兴奋，具有重要的战略意义，并且随着制造商开发创新工艺，目前正在发生转变。该项目加入了一个快速发展的英国中小企业，拥有世界领先的生物工艺开发中心。这种伙伴关系补充了优势和共同的动机，以开发用于腺相关病毒（AAV）生产的改进的解决方案，这可以被认为是基因治疗领域内的“工作马”。其目的是开发更高效、更便宜、能应对供应挑战并与客户现有设施和长期制造计划兼容的灵活流程。我们将通过结合和建立以前在该领域的工作来实现我们的目标。该项目将使用行业领先的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，并以可扩展的形式开发与临床应用兼容的生产工艺。Nanocin的低毒性特性使重复转染（DNA递送）成为可能，而这些进步，整合到商业生物反应器中，可以在生产效率和成本降低方面提供阶跃变化。利益将流向Tecrea和英国高价值的先进药物制造业，无论是区域（就潜在集群而言）还是国家。NRC将通过提高其生物处理能力而受益，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产生重大的公共卫生效益。

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.