Non-viral nanoparticles for salivary gland gene therapy

Irreversible loss of salivary gland function results in permanent hyposalivation, impacting speech, swallowing, taste, and oral health. The primary causes are irradiation damage during head and neck cancer radiotherapy and Sjögren’s syndrome, an autoimmune exocrinopathy. 

The aim of this proposal is to restore salivary gland function via a non-viral gene therapy delivery system while markedly reducing the immunogenicity risks of viral vectors. These non-viral gene delivery systems pose a significantly reduced safety risk to patients and operators, being dramatically more cost-effective, easier to manipulate, engineer and manufacture than viruses.

Silver Diamine Fluoride Use in Vulnerable Older Adults in Care Homes  

Poor oral health is common amongst care home residents in the UK, with many not being supported to maintain and improve their oral health. Silver Diamine Fluoride (SDF) is a clear liquid containing high concentrations of fluoride and silver, which work together to both prevent dental caries and arrest existing lesions. SDF is minimally invasive, requires minimal equipment, and is quick to apply. This proposal aims to undertake preliminary work for planning subsequent NIHR-funded doctoral fellowship investigating the feasibility, acceptability, and effectiveness of using SDF to both prevent and arrest carious lesions in older adults in care homes.

SMARTER composites for simultaneous pulp regeneration and tooth repair

Dental decay affects 24% of 5-year-old children in the UK but less than 10% of those affected are currently treated. Key issues exacerbating this issue have been the ban on amalgam fillings and the long treatment time (~30 min) with composites.

To address the above problems, the group has been developing SMART dental composites that can be placed directly on minimally excavated teeth. An ongoing clinical trial has shown that their optimised SMART composite, Renewal MI, can be placed in under 5 min, without drill or anaesthetic, directly on disease affected dentine but tooth bonding in non-retentive cavities was insufficient in a few clinical cases. The aim of this new study will be to determine if Renewal MI, or novel SMARTER dental composites with improved tooth bonding, can also be placed directly on the tooth pulp.  This ability would provide unique materials that can simultaneously encourage pulp regeneration and tooth restoration. The data obtained should give evidence to help justify further clinical trials of Renewal MI and get a SMARTER material optimised, manufactured, and packaged.

Mr Matt Lechner, Rob Sellar David Selwood (jointly funded with the UCLH BRC Cancer theme) 

PROTAC development for treatment of HPV-associated oral disease and cancer

Human papillomavirus (HPV)-associated oral disease and head and neck cancer poses a significant health problem. Oropharyngeal cancer has one of the most rapidly rising incidences of any cancer in high income countries, having overtaken cervical cancer in the UK.

HPV exerts its carcinogenic potential via multiple viral oncoproteins which degrade key tumour suppressor genes in infected host cells. Thereby cancer cells develop in many persistently infected patients over the years. Targeted agents (PROTAC molecules) allow the degradation of viral oncoproteins and the aim of this project is to systematically test these PROTAC molecules against two HPV oncoproteins. The agents will be refined further and their therapeutic efficacy for treating these cancers will be determined i.e. they will test whether these lead to cell death and hence could be candidate agents.