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MMBio - Marie Curie Training Network

Olivia Luige

 
Olivia_Luige_153
 

Background:
I graduated with an integrated master’s degree MChem in Medicinal and Biological Chemistry from the University of Edinburgh in 2017. I thoroughly enjoyed the opportunity to gain insights into medicinal, biological and biophysical chemistry, while also being able to get research experience in organic chemistry in academia and industry.
I completed a 12-month industrial placement in 2015/2016 at LINK, a company that manufactures reagents for oligonucleotide synthesis. My placement project involved the development of synthetic routes towards oligonucleotide building blocks and methods for their purification. I gained further experience during my final year project at university, where I tackled the synthetic challenge of regioselective C2-functionalisation of indole, which yields indole derivatives that are prevalent structural motifs in biologically active molecules. I developed a method that facilitates this transformation in the absence of directing groups under mild conditions using palladium catalysis.
Throughout my degree, I enjoyed the organic chemistry aspects of the course, while becoming increasingly interested in research with therapeutic potential. Thus, I am now eager to build on my experience in organic synthesis as well as my background in medicinal chemistry. I am honoured to be a part of the MMBio training network and contribute to the field of therapeutic oligonucleotides.

Training and Transferable Skills:

  • Organic synthesis
  • Solid phase synthesis
  • Homogeneous catalysis
  • Flash column chromatography, preparative TLC
  • HPLC, NMR, MS, IR, UV-vis

Research Projects:
My PhD concerns the chemistry of therapeutic oligonucleotides. The fundamental basis of using nucleic acids in therapy is the inhibition of target DNA or RNA expression, thus preventing the synthesis of disease-related proteins. The incorporation of chemical modifications and conjugates allows for the design of oligonucleotides (ONs) with enhanced binding characteristics, stability to enzymatic degradation and delivery to the site of action, compared to naturally occurring nucleic acids. The potential of ON therapeutics to treat serious, life-threatening diseases of genetic or viral origin is enormous, as they are uniquely equipped to carry out functions that are out of the reach of traditional small molecule drugs. ONs have, however, been under clinical investigation for several decades and have not fulfilled the early expectations. As such, it is essential to direct research efforts towards the development of new concepts and chemistries to address the key limitations of ON therapeutics.
During my PhD, I will be working on the synthesis and evaluation of new ONs that form triplexes and clamps, as well as oligonucleotide-based artificial nucleases (OBANs). I will be using peptide nucleic acid (PNA) and cell-penetrating oligonucleotides (CPOs) to synthesise ONs capable of forming triplexes with the target sequence. Such triplex forming ONs would enable the targeting of double stranded DNA or RNA by strand invasion, which would open up new targets for therapeutic intervention, such as non-coding microRNAs. I will also be working on OBANs, which are artificial enzymes designed to cleave the target RNA in a controlled site-specific manner. While our current PNA-based artificial enzymes have shown highly promising results, further development of our artificial nucleases is still required with the aim of achieving higher rates of catalytic cleavage and restriction enzyme-like specificity to allow for the use of OBANs as therapeutics in the future.

 

 

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