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Hughes, Oliver (2024) Part A: Outlining the current state of AAVs & evaluating albumins potential role in AAV stability / Part B: Comparing separation resolution of multiple SEC columns & evaluating AAV-albumin interactions. MRes thesis, University of Nottingham.

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Abstract

Part A:

Adeno-associated viral vectors are pivotal to the advancement of gene therapy, offering a promising vehicle for delivering genetic material with high efficiency and low pathogenicity. This literature review provides an analysis of the role of AAVs in gene therapy, highlighting recent developments and therapeutic outcomes across various genetic disorders. Current obstacles in AAV-based therapies such as physical stability and vector size limitations are also discussed. A significant focus is placed on the strategy of coupling AAVs with albumin to enhance vector performance and extend the expression duration of therapeutic genes. The review also outlines implications of this conjugation on the data derived from analytical techniques. It examines how this modification influences the accuracy and reliability of methods such as ELISA, qPCR, SEC-MALS and more. Findings from multiple studies provides insight into how albumin integration into AAV vectors might revolutionise gene delivery methods, potentially overcoming some of the current limitations in gene therapy research and application.

Part B:

This study compares analytical approaches for assessing the stability of adeno-associated virus (AAV) formulations. We begin by identifying the most effective size-exclusion chromatography coupled with multi-angle light scattering (SEC-MALS) column for characterizing AAV samples. Subsequently, additional techniques, including dynamic light scattering (DLS) and analytical ultracentrifugation (AUC), were employed to investigate AAV stability under varying conditions. The stability was evaluated in the presence and absence of albumin across multiple buffer. A key finding was that buffer with higher ionic strength appears to enhance AAV stability, suggesting potential benefits for long-term storage and therapeutic efficacy. These results provide valuable insights for optimizing AAV formulations for clinical and research applications.

Item Type:	Thesis (University of Nottingham only) (MRes)
Supervisors:	Jiwani, Shahwar Harding, Stephen E.
Keywords:	Human serum albumin (HSA), interactions with AAV
Subjects:	Q Science > QP Physiology
Faculties/Schools:	UK Campuses > Faculty of Science > School of Biosciences
Item ID:	79507
Depositing User:	HARDING, Prof Stephen
Date Deposited:	13 Dec 2024 04:40
Last Modified:	13 Dec 2024 04:40
URI:	https://eprints.nottingham.ac.uk/id/eprint/79507

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