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Details of Grant 

EPSRC Reference: EP/Y00289X/1
Title: GlioPrevent: PiezoMagnetic Nanoparticles to Prevent Glioma Invasion in Human Brain Organoids
Principal Investigator: RAMACHANDRA KURUP SASIKALA, Dr A
Other Investigators:
Researcher Co-Investigators:
Project Partners:
University Hospital of Dusseldorf
Department: Faculty of Life Sciences
Organisation: University of Bradford
Scheme: Standard Research - NR1
Starts: 01 March 2024 Ends: 28 February 2026 Value (£): 161,913
EPSRC Research Topic Classifications:
Biological & Medicinal Chem.
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
24 May 2023 ECR International Collaboration Grants Panel 3 Announced
Summary on Grant Application Form
Glioblastoma multiforme (GBM) is the most common malignant brain tumour in the UK, accounting for more than one in every five brain tumour diagnoses. GBM patients have a poor prognosis, with just 20% surviving more than a year and 3% surviving more than three years. GBM tumours spread quickly, with aggressive finger-like growth into important brain locations. This makes treatment challenging, with GBM tumours notoriously difficult to remove surgically. Because of this, only easily accessible cancers are removed during surgery, and radiation and chemotherapy are delivered immediately after surgery to suppress tumour growth. Hence developing a more effective therapy for GBM, that can stop the growth/invasion of finger-like GBM cells into normal brain areas is needed.

Researchers have been looking for a simple way to fix DNA mistakes to treat diseases ever since they learned that DNA changes cause cancer. A recent game-changer in this field is the CRISPR gene editing system. CRISPR can be used to cut the disease-causing genes, changing them in a way that can't be reversed by cell repair systems. This makes the cell more susceptible to therapeutic agents. Unfortunately, CRISPR has some limitations that restrict its use as a novel therapeutic. 1) The most common way to get CRISPR components into cells is with a modified virus, which can cause unwanted genetic changes, and 2) CRISPR may cut DNA outside of the intended genes and cause side effects (off-target editing).

In this project we propose a novel delivery system (PiezoMagnetic nanoparticles, PMNPs) to overcome these problems and enable targeted delivery of CRISPR to systems modelling the human brain.

PMNPs are materials that can be used to transport therapeutic agents into cells. The PMNPs are coated with the therapeutic agent, injected into the body and directed to the target cells using a magnet or ultrasound. In this work, we will produce a PMNP coated with a CRISPR system designed to target PLK1 and NeK 2 genes, which are associated with GBM. We believe preventing these genes from functioning will stop the growth of GBM cells, offering a potential avenue for future treatments. To increase the specificity of the PMNP to the GBM, a unique and clinically relevant targeting agent will also be applied to the carriers. These will be tested in small models of the human brain known as organoids. The treated PMNPs will be applied to models containing GBM and normal cells and the growth of the GBM cells will be measured over time.

The results will lay the groundwork for the further development of PMNPs as a delivery system and organoids as a model testing system.

The collaborators (the University of Bradford and University Hospital Dusseldorf) will also convene a panel of glioblastoma experts to advise on the research and to form the basis of a glioblastoma research network. The collaborators will work together to lead meetings and events to promote and drive forward further glioblastoma research.

Key Findings
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Potential use in non-academic contexts
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Date Materialised
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Organisation Website: http://www.brad.ac.uk