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

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. Polymer induced self-assembly (PISA) will be used to produce these polymers from a range of monomers. 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 (Fielding Lab) 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.

www.broadspectrumantivirals.com
https://www.fieldinglab.co.uk

Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships