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(BBSRC DTP) Synthesis and identification of highly efficient polymeric nanoparticles for transfection of cells


Project Description

Gene therapy transfers genetic material into cells to provide new functions, including as potential interventions and treatments for a wide range of human diseases. Polymers can be used in this instance, providing advantages in scalability and precision control. For gene delivery, polyamines are often preferred: the positively charged nature of the polymer allows for electrostatic binding to nucleic acids, additionally providing protection to the nucleic acids by buffering pH during endocytosis. These polyamines however, have poorly controlled degradation profiles and are sometimes highly toxic. Accessing a step-change in gene-therapy delivery systems requires a bottom-up rethink of the polymer nanoparticle framework.

Thus we propose to develop biodegradable polymers that will allow for efficient and effective transfection of nucleic acids to cells. These polymers will be designed for binding to nucleic acids and to provide protection during endocytosis. Ring opening polymerisation (ROP) will be used to produce these degradable polymers from cyclic esters, diesters and dioxolanes. Using poly(ethylene glycol) (PEG) functionalised dye molecules (produced in the Jones Lab) as the initiating species a dye labeled polymeric delivery system will be produced which will allow for in-vitro tracking and imaging. These will be assembled into polymeric nanoparticles with nucleic acids encoding for GFP expression (Gene Editing Unit, UoM). Fluorescence microscopy and FACS will be used to assess the transfection efficiency of each PNP in order to identify the most potent transfection PNP. Impact-driven final project stages will exploit specific nucleic acid sequences for delivery to macrophages (in-vitro), to be investigated in-vivo through collaborative efforts.

Jones Lab - http://www.broadspectrumantivirals.com
Shaver Lab - https://greenmaterialslaboratory.com

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

How good is research at The University of Manchester in Electrical and Electronic Engineering, Metallurgy and Materials?
Metallurgy and Materials

FTE Category A staff submitted: 44.00

Research output data provided by the Research Excellence Framework (REF)

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