###Synthesis and Application of Photocaged DNA and RNA Technologies

Project ID: 2228bd1153 (You will need this ID for your application)

Research Theme: Physical Sciences

UCL Lead department: Chemistry

Department Website

Lead Supervisor: Michael Booth

Project Summary:

DNA and RNA are central to life and form the basis for many therapeutic and experimental technologies. Targeted activation of nucleic acids would allow for precise control of their function in many applications, including synthetic biology, biotechnology, and therapeutics. Control with non-invasive stimuli – remote control – is ideal for this targeted activation. Light is a desirable remote stimulus, which allows for precise, bioorthogonal, and spatiotemporal control. The advantages of light as a stimulus are that it can be applied with micrometre precision and offers multiple wavelengths for potential orthogonal or sequential activation of different species. We have previously generated light-activated DNA that shows tight regulation of cell-free protein expression using short wavelengths of light. However, longer wavelength activation (for instance near-IR) has distinct advantages for future application, for instance higher tissue penetration and lower cytotoxicity. In this project we will synthesise long wavelength photocages followed by their incorporation into a range of nucleic acid technologies. This work will take advantage of our previous and current work on attaching different photocages to multiple locations on nucleic acids such as cell-free DNA templates, antisense oligonucleotides, and plasmids. Control of activity will be measured in both cell-free and cellular systems. When using cellular systems, methods of cellular delivery of nucleic acids will be incorporated into the design of the system. Developing this suite of long wavelength light-activated nucleic acids will allow researchers to reimagine the way they study living systems and develop therapeutics. For this project, we are looking for a student who understands chemistry and wants to apply their knowledge towards biological and medical problems.