Developing non-viral polymeric agents to deliver genome engineering technology for breast cancers

Research output: ThesisDoctoral Thesis

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Abstract

Tools for editing the genome and epigenome represent a new frontier in targeted therapeutic intervention. CRISPR-based technology enables precise and robust genetic and epigenetic modulation for virtually any potential target gene. However, clinical implementation of these technologies is problematic as safe and effective delivery of all CRISPR components to the target tissue remains a challenge. In this work, polymeric agents were designed and synthesised to systematically optimise delivery of gene therapeutics. The modular synthetic approach allowed variation in polymer properties, and enabled the design of a highly efficient transfection agent which was further utilised for the delivery of CRISPR/dCas9 for the activation of two tumour suppressor genes in both in vivo and in vivo breast cancer models. The modular design of the polymer further allowed fundamental research into the delivery of multiple DNA plasmids, the role of charge density in polymer dynamics and diffusion, and the delivery of proteins.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • The University of Western Australia
Supervisors/Advisors
  • Blancafort, Pilar, Supervisor
  • Swaminatha Iyer, Iyer, Supervisor
  • Norret, Marck, Supervisor
Thesis sponsors
Award date30 Dec 2019
DOIs
Publication statusUnpublished - 2019

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