Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597479
Title: The potential of polyethylene imine derivatives as transfection reagents
Author: Chapman, M. R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2007
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Abstract:
This work aimed to address these issues by taking a novel approach to both the design and analysis of a library of transfection reagent derivatives. The library was produced by derivatisation of polyethylene imine (PEI), already a relatively efficient transfection reagent.  However, rather than viewing derivatisation as an all or nothing process, our libraries apply derivatisation in a stepwise fashion to completely explore the chemical space. By using combinations of three simple derivatisations (methylation, benzylation and dodecylation), a large range of properties are produced from limited chemical diversity, including some polymers which rival the commercial gold standards in activity. The approach taken to analysis of the library properties is also new to the field. The properties most relevant to activity as a transfection reagent (expression of a reporter gene and toxicity) are viewed as the result of a series of steps each of which may have differing and conflicting requirements. The design of high-throughout assays for these properties and for DNA binding is described as are the clear relationships observed between these activities and derivatization levels. Using the DNA binding assay a start is made towards understanding how chemical space maps into the functional space of transfection and toxicity. Measurements of complex size are used to explain some requirements for transfection with polyethylenimine and the effect of derivatisation on DNA binding is investigated further to produce an account of the transfection process from formation of the transfection complex through to cell entry.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.597479  DOI: Not available
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