Building DNA nanopores for drug delivery transport

Lead Research Organisation: University College London
Department Name: Chemistry

Abstract

This PhD project will build DNA pores with the advanced function to regulate the transport of cargo across membranes for drug delivery devices and synthetic biology (Nat. Nanotechnol. 11, 152-156 (2016)). It is multidisciplinary and incorporates elements of chemical biology, nanobiotechnology, and biophysics. Student will obtain training in DNA nanotechnology.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509577/1 01/10/2016 30/09/2021
1930798 Studentship EP/N509577/1 25/09/2017 30/06/2021 William Lawrence Whitehouse
 
Description After approximately one year of my 3-year EPSRC funded PhD at University College London, I published my research findings in the ACS journal of Bioconjugate chemistry, regarding how 'Cholesterol Anchors Enable Efficient Binding and Intracellular Uptake of DNA Nanostructures' https://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00036. I have since tested the DNA nanopore used in the study referenced above, as well as other DNA nanopores devised in the Howorka laboratory for activity in Hela cells and have found that these structures do not appear to be able to permeabilise cellular membranes. The focus of my work has since shifted, with agreement from my primary supervisor, to focus on integrating cell penetrating peptides with DNA nanostructures - to investigate drug delivery transport via membrane destabilisation and pore-formation. My initial work was conducted between University College London and the National Physical Laboratory. I have gained skills with DNA nanostructure design, fabrication, characterisation as well as cellular metrology methods including confocal microscopy and fluorescence activated cell sorting (FACS). I plan to continue building skills in this area and working between my host institutions to carry out experiments in-line with my project work, which include the fabrication and or use of synthetic lipid vesicles, dynamic light scattering, FACS, microscopy, peptide synthesis, bioconjugation chemistry, chromatography and mass spectrometry.
Exploitation Route My initial findings, published soon after completion of my first year of study have been published in the ACS journal of Bioconjugate chemistry.
This work has since been cited three times. I hope to publish findings again before the funding finishes.
Sectors Pharmaceuticals and Medical Biotechnology

URL https://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00036