Star polymers for gene delivery

Lead Research Organisation: Imperial College London
Department Name: Materials

Abstract

Gene delivery is an important challenge for the realisation of any genetic therapy. One of the main problems is that the charge of genetic material, be it DNA or RNA, is the same as the surface of the cell. Hence, shuttling these polymers inside the cell to do their job requires to overcome a large energetic barrier due to electrostatic repulsion. One of the ideas to solve this issue is to form a complex between the genetic material and a poly-cation so as to neutralise the overall effective charge. However, care must be taken with using this simple concept because the strength of the interaction must still be tuned: If the complex is too stable, once inside the cell it will not allow DNA or RNA to be released and interact with the cellular machinery required for the therapy to be effective. If not stable enough, the genetic material will not be shuttled inside the cell in the first place.
In this project, we aim to use coarse-grained modelling and molecular dynamics to study the stability of complexes between positively charged star polymers and small DNA sequences representative of what are usually employed in genetic therapy. Our goal is to determine how synthetically tuneable parameters of the poly-cation affect the overall binding free-energy, and hence the complex stability. Results from simulation will be able to provide rational guidelines to our experimental collaborators.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509486/1 01/10/2016 31/03/2022
2275313 Studentship EP/N509486/1 30/09/2017 30/09/2021 Debesh Mandal