Coordination Funds

抗体工程、基因组测序、基因操作和基因传递等关键技术的重大进步，使开发新的、创新的眼部疾病基因治疗方法成为可能。这在voretigene neparvovec的案例中得到了很好的例证，voretigene neparvovec是目前唯一上市的眼部基因疗法，为RPE65基因突变引起的视网膜病变患者提供了治疗选择。虽然基于腺相关病毒（AAV）载体的基因补充疗法是治疗其他常染色体隐性视网膜疾病的有效概念，但它不能用于治疗更具挑战性的病例，如常染色体显性遗传的功能获得突变。同样，AAV载体的载货能力有限，不支持较大基因的转移，这限制了AAV技术的广泛适用性，也不允许解决由大基因突变引起的挑战性病例。其他遗留的挑战涉及遗传原因不明确的视网膜疾病，如年龄相关性黄斑变性（AMD）或糖尿病性视网膜病变（DR）。目前可用的AMD和DR对症治疗需要通过眼内注射反复给药，不能阻止疾病进展。基因治疗概念的应用可以克服现有对症治疗的局限性，并为这些视网膜疾病开发潜在的一次性治疗方法。为了解决这些未满足的需求，拟议的研究单位将专注于开发新的技术和方法，为具有挑战性的视网膜疾病提供变革性的基因治疗解决方案。该联盟将以集中的方式利用关键的专业知识和诀窍，克服目前的障碍，广泛成功地应用基因疗法来治疗具有挑战性的遗传性和获得性视网膜疾病。

Significant advancements in key technologies like antibody engineering, genome sequencing, gene manipulation, and gene delivery made it possible to develop novel, innovative gene therapy approaches for ocular disorders. This is nicely exemplified in the case of voretigene neparvovec, the first and currently only marketed ocular gene therapy, which offers a treatment option for patients with retinopathy caused by mutations in the gene RPE65. While adeno-associated virus (AAV) vector-based gene supplementation therapy is a valid concept to treat additional autosomal recessive retinal disorders, it cannot be applied to treat more challenging cases such as gain-of-function mutations with autosomal dominant inheritance. Similarly, the limited cargo capacity of AAV vectors does not support transfer of larger genes, which limits the broad applicability of the AAV technology and does not allow to address the challenging cases caused by mutations in large genes. Other remaining challenges relate to retinal diseases with unclear genetic cause such as age-related macular degeneration (AMD) or diabetic retinopathy (DR). Currently available symptomatic treatments for AMD and DR need to be repeatedly administered via intraocular injection and do not halt disease progression. Application of gene therapy concepts could allow to overcome the limitations of available symptomatic treatments and to develop potentially curative one-time treatments for these retinal diseases. To address these unmet needs, the proposed Research Unit will focus on the development of novel techniques and approaches to provide transformative gene therapy solutions for challenging retinal disorders. The consortium will leverage the key expertise and know-how in a focused manner to overcome current hurdles for the broad successful application of gene therapy to treat challenging genetic and acquired retinal diseases.