Thesis

Novel polyamino acid based vesicles in gene delivery

Creator
Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2001
Thesis identifier
  • T10388
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Advances in genetic research have revealed the genetic cause of many disorders, with various genes being discovered and linked to a vast range of diseases. This has increased the interest in gene therapy as a form of treatment for many disorders. A major obstacle to the success of gene therapy is the development of an effective delivery system. Various systems have been investigated for their ability to deliver genetic material into cells. However, all have disadvantages that need to be overcome before gene therapy can be thought of as a realistic treatment. In this study, characterisation of novel amino acid based polymeric vesicles, POP and PLP, was carried out to establish their potential as gene delivery agents. The amphiphilic polymers, POP and PLP, were produced by the covalent attachment of polyethylene glycol and palmitoyl groups onto poly-L omithine and poly-L-lysine, respectively. These novel polymers were able to assemble into vesicles when sonicated in the presence of cholesterol. Physical characterisation of POP and PLP polymers and the resulting vesicular systems was carried out. In vitro investigations involved DNA condensation and biocompatibility studies, as well as transfection studies using both the P-galactosidase and luciferase transfection assays. POP and PLP systems were also tested in vivo to determine expression levels of genetic material in mouse liver and lung tissue. In an attempt to target POP and PLP systems to liver cells, a galactosamine targeting moiety was synthesised. This was formulated with POP and PLP and analysis was carried out as for the POP and PLP vesicles. POP and PLP systems are capable of condensing DNA and can transfect various cell lines to a higher level than DNA alone. They were shown to be biocompatible and can be injected intravenously into mice without producing toxic effects, where they appear to produce some protein expression.
Advisor / supervisor
  • Uchegbu, Ijeoma F.
Resource Type
DOI
EThOS ID
  • uk.bl.ethos.248254
Embargo Note
  • This thesis is currently under moratorium due to copyright restrictions. If you are the author of this thesis, please contact the Library to resolve this issue.

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