PhD Project - Messenger: mRNA-based therapies with Enhanced Site Selective Expression using Cold Plasma and Ultrasound

Job Description

Overview
mRNA presents several advantages over traditional viral vector and DNA-based approaches including relatively simple scaling of manufacturing, potent but short lasting and relatively non-immunogenic protein expression, and limited capacity for host cell genome integration events occurring. However, while the current approach is effective for inducing vaccine responses, widespread tissue re-engineering will rely on higher expression and a capacity to switch on and off expression in different cells and tissues. This project will explore the use of Cold Plasma and ultrasound to enhance intra-tumoral delivery and cell uptake of encapsulated mRNA therapies using preclinical models.

Research Question
mRNA therapies have desirable manufacturing and safety characteristics including scalable production and no genomic integration. However, fine control of expression in tissues is challenging. Can we use localised energy-based medical technology such as ultrasound and Cold Plasma to augment tissue distribution and expression from mRNA-based therapeutic genes and reporter genes?

Aim and Objectives
The aim of the project (MESSENGER) is to demonstrate the feasibility of using focussed energy in the form of cold plasma and ultrasound to improve mRNA-based therapy diffusion into tumours and enhance uptake in cells, thereby locally regulating expression.
Objectives
1. Establish and optimise a T7 mRNA synthesis protocol for selected reporter and therapeutic genes.
2. Synthesise, characterise and optimise redox-sensitive liposomes.
3. Measure enhanced uptake and expression of mRNA cargo using plate-to-pin and dielectric barrier plasma devices.
4. Quantify diffusion kinetics in 3D tumour spheres using 25kHz and 45kHz Ultrasound with tunable power settings.
5. Establish and characterise cavitation induced liposomal rupture to further aid gene delivery.
6. Optimise and compare conditions in mixed culture models.

Student requirements for this project
minimum 2.1 BSc in biochemistry, biotechnology, bioengineering, or related.

Funding details
Student Stipend € 18 500
Materials/ Travel etc € 2 600
Fees € 4 500

Applicants for this project are required to complete an Expression of Interest (www.dit.ie/media/documents/study/postgraduateresearch/EOI%20Form.doc) and email it to [email protected]