iAds: Intelligent Design Of Adenovirus Vectors

先进的疗法，特别是基因疗法，在治疗几乎没有选择的疾病方面拥有巨大的潜力。有效的基因转移与载体的效力有着内在的、不可妥协的联系。部分由于缺乏适用于特定应用的传递系统，太多的基因疗法的成功是有限的。在过去的二十年里，病毒载体的发展取得了巨大的进步。重要的是，这一进展还确定了降低疗效的媒介特征和生物因素。虽然有限的疗效与所有载体平台相关，但对腺病毒来说，这一点更为紧迫，因为它们具有如此大的潜力。在某些情况下，宿主反应和不完善的靶向阻碍了腺病毒载体的开发，用于需要长期转基因表达的治疗。我们的多方面联盟提出了一种创新的方法来克服这些限制，并构建了一条开发用于临床基因转移的改进载体的途径。通过整合法国、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、心脏生物学和生物处理方面的专业知识，我们将在电子设计的智能腺病毒载体(IAds)中创建。我们的颠覆性概念摒弃了从自然产生的腺病毒中开发载体的经典方法。取而代之的是，一种专有腺病毒类型将被连续剥离不需要的成分，以创建一组iAD，然后这些iAD将被设计成心脏和大脑特异的靶向。我们的联盟融合了学术独创性和中小企业/制药制造，将允许无缝临床翻译。在EIC计划的支持下，我们的开创性方法将彻底改变基因转移，并通过一个充分利用病毒载体潜力的平台，在未得到满足的医疗需求领域产生解决方案。

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.