Development of therapeutically useful Human Artificial Chromosomes for gene delivery and optimal gene expression

基因治疗是一种令人兴奋的治疗遗传性疾病的新形式，旨在从源头——即受影响的基因——提供长期的问题纠正。基因治疗面临的最大技术障碍是如何将治疗基因高效、安全地输送到患者细胞中。许多基因治疗方案目前正在临床试验中。这些方案主要基于使用减毒病毒来传递基因，在感染、免疫反应和种系修饰方面对患者存在潜在风险。我们已经开发了一种不需要使用病毒的基因传递新技术的第一阶段。这项技术是基于人类人工染色体的产生，这是自然发生的染色体的小版本，携带着我们细胞内所有的基因。这些人造染色体的安全性来自于它们的工程完全使用了人类材料。与病毒疗法相比，这些人工染色体还有其他优势，包括允许携带大基因，并在一次治疗中提供永久治愈。我们已经成功构建、发表了一批第一代人类人工染色体，并申请了专利。目前的项目旨在完成该技术进一步发展的下一个概念验证里程碑。具体来说，我们建议证明人工染色体携带基因的能力，并在细胞和动物模型中提供这些基因的可持续表达。这项研究的成功将使该技术迅速进入商业化和临床试验，作为基因传递和基因治疗的新改进工具。

Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in terms of infection, immune response, and germline modification. We have developed the first stage of a new technology for gene delivery that does not require the use of viruses. This technology is based on the generation of human artificial chromosomes, which are smaller versions of the naturally occurring chromosomes that carry all the genes inside our cells. Safety in these artificial chromosomes comes from the use of entirely human materials for their engineering. These artificial chromosomes also have other advantages over the viral approaches, including allowing large genes to be carried, and providing a permanent cure in a single treatment. We have already successfully constructed, published, and patented a number of first-generation human artificial chromosomes. The current project aims to complete the next proof-of-concept milestone towards the further development of this technology. Specifically, we propose to demonstrate the ability of the artificial chromosomes to carry genes and provide sustainable expression of these genes in cells and in animal models. Success in this study will allow the technology to proceed rapidly into commercialisation and clinical trial as a new improved tool for gene delivery and gene therapy.