Multiplexed in vivo optimisation of non-toxic gene transfer agents.

无毒基因转移剂的多重体内优化。

• 批准号: G0801908/1
• 负责人: Mark Bradley
• 金额: $ 78.83万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801908%2F1
• 关键词: Multiplexed; vivo; optimisation; non; toxic

Putting material into cells is very challenging as cells have natural barriers that prevent the entry of most foreign materials. However being able to put specific genetic material (DNA) into human cells would have immense medical applications. For example the genetic material could be used to correct a defective gene (such as in cystic fibrosis), fight viral infection or prevent the growth of cancers.This project aims to develop tools that allow the rapid discovery of delivery devices that enable the efficient delivery of DNA into cells. One such tool is so-called multiplexed analysis where we will prepare 100 different combinations of DNA and carrier materials and then analyze these in such a way in which a hundred different compounds will be evaluated at one time. The winner will be compound that enters the cell most efficiently. Multiplexing is of course a well known term in relations to movie theatres with multiple screens. The analogy here is that we have 100 movies running (the analogy is that these are the 100 formulations we are examining), we admit 10,000 people (these by analogy are the cells) and analyze the distribution of people (cells) i.e. what was the most favourite film. A second element of this project is the development of delivery devices that are non-toxic and degrade naturally. Extending our movie analogy further we are looking for the one that will leave a positive lasting impression on the viewer (which may not of course be the movie that had the greatest audience!). Cystic fibrosis (CF) is a genetic disease affecting over 7000 individuals in the UK. Patients suffer frequent bacterial infections which lead to more and more lung damage. While there have been great improvements in CF treatment, lung disease leads to early death with a life expectancy at birth of about 30 years. Gene therapy, involving replacement of the defective CF gene with a working copy, has the potential to greatly improve the health of CF patients. Gene therapy offers the possibility of improving the patient?s prospects dramatically as well as reducing the disease s economic impact. This project is focused on producing better gene therapy formulations for the treatment of cystic fibrosis. However, indirectly, the formulation and characterization of novel gene transfer reagents would feed into the gene therapy field in general, and such reagents may find application in the treatment of other genetic disorders.

将材料放入细胞中是非常具有挑战性的，因为细胞具有天然屏障，可以防止大多数异物进入。然而，能够将特定的遗传物质（DNA）放入人类细胞将具有巨大的医学应用。例如，遗传物质可用于纠正有缺陷的基因（如囊性纤维化），对抗病毒感染或预防癌症的生长。该项目旨在开发工具，允许快速发现能够将DNA有效递送到细胞中的递送装置。其中一个工具是所谓的多重分析，我们将准备100种不同的DNA和载体材料的组合，然后以一种同时评估100种不同化合物的方式分析这些组合。赢家将是最有效进入细胞的化合物。多路复用当然是与具有多个屏幕的电影院有关的众所周知的术语。这里的类比是，我们有100部电影正在播放（类比是，这些是我们正在检查的100种配方），我们接纳10，000人（通过类比，这些是细胞）并分析人（细胞）的分布，即最喜欢的电影是什么。该项目的第二个要素是开发无毒和自然降解的输送装置。进一步扩展我们的电影类比，我们正在寻找一个会给观众留下积极持久印象的电影（当然这可能不是拥有最多观众的电影！）。囊性纤维化（CF）是一种遗传性疾病，影响英国7000多人。患者频繁遭受细菌感染，导致越来越多的肺部损伤。虽然CF治疗已经有了很大的改进，但肺部疾病导致早死，出生时的预期寿命约为30岁。基因治疗，包括用工作拷贝替换有缺陷的CF基因，有可能大大改善CF患者的健康。基因治疗提供了改善病人的可能性？的前景，以及减少疾病的经济影响。该项目的重点是生产更好的基因治疗配方，用于治疗囊性纤维化。然而，间接地，新的基因转移试剂的配制和表征通常会进入基因治疗领域，并且这样的试剂可以在其他遗传疾病的治疗中找到应用。