Structural and biological insights into novel adenovirus-based platforms for therapeutic applications

Mundy, Rosie 2025. Structural and biological insights into novel adenovirus-based platforms for therapeutic applications. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Human adenoviruses (HAdV) cause a range of infection types, including ocular, respiratory and gastrointestinal infections. HAdV are divided into seven species, denoted A-G. The genome of HAdV is highly amenable to engineering, which makes HAdV interesting as therapeutic vectors for gene therapy, vaccination and oncolytic virotherapy. Current work to utilise HAdV as therapeutic vectors has focused predominantly on adenovirus type 5 (HAdV-C5). As a common pathogen, there are high levels of pre existing immunity against this virus, so a HAdV-C5 based vector may be cleared by the immune system before any therapeutic benefit can be achieved. As a result, there is growing interest in other, low seroprevalence HAdV serotypes. Species D adenoviruses (HAdV-D) have low global seroprevalence, underscoring their potential for development as therapeutic vector platforms. HAdV-D serotypes are understudied, and key research is required to ensure their safe and effective development as therapeutic vectors. The work in this thesis aims to add to the expanding body of knowledge surrounding HAdV-D serotypes, to aid in their clinical development as therapeutic vectors. Structural insights have proven critical to detailing virus: host interactions therefore an integrated structural biology approach was utilised. Receptor interactions were explored to identify a species wide ability to engage sialic acid for cell entry by HAdV D fiber-knob proteins. Recent improvements in technology were also exploited throughout this project to investigate low seroprevalence HAdV-D serotypes. Cryo-electron microscopy and long read sequencing techniques were utilised to produce a high resolution reconstruction of HAdV-D10, and long read sequencing techniques highlighting key transcriptomic differences to HAdV-C5. Finally, receptor interactions of HAdV-D49 were investigated, highlighting potential engagement of sulphated glycans as important for cell engagement. Taken together, these data provide insights into HAdV-D for the purpose of future development of novel adenovirus-based therapeutic platforms.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Medicine
Date of First Compliant Deposit:	11 March 2026
Last Modified:	11 Mar 2026 14:19
URI:	https://orca.cardiff.ac.uk/id/eprint/185659

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