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SYNTHESIS AND DEVELOPMENT OF ZWITTERIONIC PEI (zPEI) FOR OPTIMIZED DELIVERY OF NUCLEIC ACIDS

Gene therapy holds promise for the treatment a wide range of diseases ranging from cystic fibrosis to cardiovascular disease to cancer. The need for safe and efficient gene delivery methods remains the primary barrier to human gene therapy. Non-viral vector materials, including polymers, can be designed to be biocompatible and non-immunogenic, but lack the efficiency to be clinically relevant. Gene therapy awaits the development of new materials that are both safe and efficient. Here, we have synthesized a series of modified zwitterionic polymers based on the common transfecting agent polyethylenimine (PEI). Using a variety of biochemical and biophysical methods we have studied structure-function relation in zPEI-DNA as a function of percent modification. Our results show significant structural rearrangements in the DNA condensates with increasing zwitterionic character. The percent zwitterionic modification determines not only DNA packaging but the serum stability of the resulting polyplexes with more highly modified zPEI releasing DNA more readily.

Identiferoai:union.ndltd.org:uky.edu/oai:uknowledge.uky.edu:chemistry_etds-1096
Date01 January 2017
CreatorsDuke, Joseph Raleigh, III
PublisherUKnowledge
Source SetsUniversity of Kentucky
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses and Dissertations--Chemistry

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