iAds: Intelligent Design Of Adenovirus Vectors

先进疗法，特别是基因疗法，在治疗几乎没有选择的疾病方面具有巨大潜力。有效的基因转移与载体功效有着内在且不可分割的联系。部分由于缺乏适合特定应用的合适的递送系统，太多基因疗法的成功受到限制。在过去的二十年中，病毒载体的开发取得了巨大进展。重要的是，这一进展还确定了降低功效的载体特征和生物因素。虽然有限的功效与所有载体平台相关，但对于腺病毒而言更为紧迫，因为它们具有巨大的潜力。在某些情况下，宿主反应和不完善的靶向阻碍了需要长期转基因表达的疗法的腺病毒载体的开发。我们的多方面联盟提出了一种创新方法来克服这些限制，并构建一条开发改进临床基因转移载体的途径。通过协同法国、荷兰、英国、西班牙和瑞典在结构生物学、受体参与、神经生物学、心脏生物学和生物加工方面的专业知识，我们将创建计算机设计的智能腺病毒载体（iAd）。我们的颠覆性概念放弃了从天然腺病毒开发载体的经典方法。相反，一种专有的腺病毒类型将被连续地去除不需要的元素，以创建一个 iAd 库，然后将其设计为针对心脏和大脑特定的目标。我们的联盟融合了学术独创性和中小企业/制药制造，将实现无缝的临床转化。在 EIC 计划的支持下，我们的突破性方法应该彻底改变基因转移，并通过充分利用病毒载体潜力的平台，为未满足的医疗需求领域提供解决方案。

Advanced therapies, and in particular gene therapies, hold great potential for treating diseases for which few options exist. Efficient gene transfer is inherently and intransigently linked to vector efficacy. Partially due to the lack of suitable delivery systems for particular applications, the success of too many gene therapies is limited. Over the last two decades, immense progress has been made in the development of viral vectors. Importantly, this progress has also identified vector characteristics and biological factors that decrease efficacy. While limited efficacy is relevant for all vector platforms, it is more pressing in the case of adenoviruses because they have so much potential. In some cases, host responses and imperfect targeting have stunted adenovirus vector development for therapies that require long-term transgene expression. Our multi-faceted consortium proposes an innovative approach to overcome these limitations and to construct a pathway for developing improved vectors for clinical gene transfer. By synergising French, Dutch, British, Spanish and Swedish expertise in structural biology, receptor engagement, neurobiology, cardiobiology, and bioprocessing, we will create in silico designed intelligent adenovirus vectors (iAds). Our disruptive concept abandons the classical approach of developing vectors from naturally occurring adenoviruses. Instead, a proprietorial adenovirus type will be serially stripped of unwanted elements to create a bank of iAds, which will then be engineered for heart- and brain-specific targeting. Our consortium blends academic ingenuity and SME/pharma manufacturing that will allow seamless clinical translation. With the support of the EIC Programme, our ground-breaking approach should revolutionise gene transfer and generate solutions in areas of unmet medical need via a platform that exploits the full potential of viral vectors.