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

适配子是由单链DNA或RNA分子组成的快速发展的寡核苷酸工具，由于其独特的三维结构，几乎能够与任何选择的配体结合，具有高亲和力和特异性。适配子正在从一个简单的研究工具迅速成熟为一项具有巨大商业潜力的重大技术。适配子提供了一种替代传统治疗方法的有前景的替代方法，因为它们不会引起免疫原性或毒性，并且可以很容易地进行修饰，以增加其在生物环境中的稳定性。此外，适配子的生产速度快，成本相对低廉。这些显著的特性反映在第一种基于适体的治疗剂(Macugen)上，该药被临床批准为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1，2，3进入市场。在本博士学位论文中，我们将研究适体的潜力，以控制细胞过程和靶向被认为是不可药物的生物标记物；这在药理学上是不能被靶向的。这些靶标中有很大一部分属于转录因子(TF)的类别，它们的调节现在是癌症研究中的关键挑战之一，需要创新和新技术的开发。因此，我们将探索是否可以通过单链RNA适配子抑制转录调控。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。

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.