Novel aptamer tools for Synthetic Biology and the control in cell and gene therapies

用于合成生物学以及细胞和基因治疗控制的新型适体工具

• 批准号: 2745298
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2745298
• 关键词: Novel; aptamer; tools; Synthetic; Biology

Aptamers are rapidly developing oligonucleotide tools that consist of single stranded DNA or RNA molecules that are capable of binding nearly any ligand of choice with high affinity and specificity due to their specific three-dimensional structures. Aptamers are rapidly maturing from a simple research tool into a major technology with huge commercial potential. Aptamers provide a promising alternative to conventional therapeutic approaches as they elicit no immunogenicity or toxicity and can be easily modified to increase their stability in biological environments. Moreover, aptamers can be produced quickly and relatively inexpensively. These remarkable properties are reflected by the first aptamer-based therapeutic agent (Macugen) clinically approved as a drug for treating a form of macular degeneration. In recent years, more and more researchers and pharmaceutical companies are realizing the enormous potential of aptamers and aptamer-based products will enter the market in the near future 1,2,3. In this PhD we will investigate the potential of aptamers to be developed for controlling cell processes and targeting biomarkers that are considered 'undruggable'; that cannot be targeted pharmacologically. A large percentage of these targets fall under the category of transcription factors (TFs) and their modulation is now one of key challenges in cancer research that requires innovation and the development of new technologies. Therefore, we will explore whether we could suppress transcriptional regulators via a single-stranded RNA aptamers. We will also develop aptamer based synthetic gene regulatory circuits for control of cellular processes.

适体是快速发展的寡核苷酸工具，其由单链DNA或RNA分子组成，由于其特定的三维结构，其能够以高亲和力和特异性结合几乎任何选择的配体。适体正从一个简单的研究工具迅速成熟为具有巨大商业潜力的主要技术。适体为常规治疗方法提供了一种有前途的替代方案，因为它们不会引起免疫原性或毒性，并且可以容易地进行修饰以增加它们在生物环境中的稳定性。此外，适体可以快速且相对便宜地产生。这些显著的特性反映在第一种基于适体的治疗剂（Macugen）临床上被批准为用于治疗一种形式的黄斑变性的药物。近年来，越来越多的研究人员和制药公司意识到适体的巨大潜力，基于适体的产品将在不久的将来进入市场1，2，3。在这个博士学位中，我们将研究开发用于控制细胞过程和靶向生物标志物的适体的潜力，这些生物标志物被认为是“坚固的”;不能被靶向。这些靶点中有很大一部分属于转录因子（TF）类别，它们的调节现在是癌症研究的关键挑战之一，需要创新和开发新技术。因此，我们将探索是否可以通过单链RNA适体抑制转录调节因子。我们还将开发基于适体的合成基因调控电路，用于控制细胞过程。