Rotaxane-DNA · Rotaxane-Oligonucleotides: Stimuli-Responsive Mechanically Interlocked Architectures to Control Oligonucleotide Activity and Gene Transcription
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-06-07 → 2020-11-01
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Rotaxane-Oligonucleotides: Stimuli-Responsive Mechanically Interlocked Architectures to Control Oligonucleotide Activity and Gene Transcription
During this MSCA, I helped develop a new type of synthetic but biocompatible DNA. The key innovative feature of my work was that the DNA molecule was wrapped in a circular molecule to create a structure called a rotaxanes. The key challenge I addressed in my project was how to make this rotaxane-DNA and a preliminary investigation of its properties. I demonstrated that the ring around the DNA changes its biological properties and developed new rings that can be used to change the properties of rotaxane-DNA further. This rotaxane-DNA is an exciting platform for development of tools for studying the behaviour of cells and new therapeutic molecules based on DNA and RNA. The overall objectives of the project, which will continue beyond my project, are to deliver rotaxane-DNA and RNA that can be used to control protein expression in cells and whole organisms.
Data: CORDIS, © European Union
Project objective
Recently, DNA-mimics have been developed in which a natural phosphate unit linking the DNA bases is replaced with a non-natural triazole. This DNA-mimic behaves identically to natural DNA, presenting an opportunity I will exploit during this Fellowship: my mentor, Prof Goldup, has developed chemistry that wraps a ring-shaped molecule (macrocycle) around such triazole links to produce interlocked molecules called rotaxanes. These molecules are perhaps most famous as components of molecular machines, culminating in the 2016 Nobel Prize for chemistry part-awarded to Stoddart and Sauvage, but the mechanical bond also offers opportunities to control the chemistry of the interlocked components.Combining these approaches, I will create interlocked rotaxane-DNAs to study how threading the macrocycle onto DNA affects the biological function of the nucleic acid. During this Fellowship I will develop the first generation of rotaxane-oligonucleotides, study their properties and utilize the mechanical bond to regulate their biological activity. These interlocked oligonucleotides will be demonstrated as versatile new tools for chemical biology through examples of controlled gene expression and therapeutic siRNA applications.
Original text from CORDIS.
Participants
- UNIVERSITY OF SOUTHAMPTON · SOUTHAMPTONCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union