Oligonucleotides, short nucleic acids of ≈ 100 bases and under, are therapeutics of great interest because of their ability to regulate gene expression and improve outcomes in diseases like cancer and atherosclerosis. However, they are vulnerable to degradation by enzymes in the body that can limit their effectiveness. Encapsulating oligonucleotides inside core-corona structures called polyelectrolyte complex micelles can be accomplished by mixing them with a block copolymer containing one neutral, hydrophilic block and one charged block. Using a micelle as a vehicle is a powerful way of protecting oligonucleotides while enabling their targeted delivery to a disease site via the attachment of targeting molecules to the micelle corona. Understanding how oligonucleotides interact with charged polymers, and how the polymers themselves affect micelle shape, size, and internal structure, are of fundamental importance to the process of efficiently and intelligently designing these micelles. By combining multiple physical characterization techniques including optical microscopy, FRET, circular dichroism, and FTIR, we can characterize bulk complexes of oligonucleotides with cationic homopolymers. By combining small-angle X-ray scattering, light scattering, and cryogenic transmission electron microscopy (cryo-TEM) we can characterize structures formed when oligonucleotides complex with oppositely charged block copolymers. These multimodal characterization schemes will increase the rigor of our investigations and our confidence in their results. Our main goals are to characterize bulk complexes of oligonucleotides and peptides to gain insight into the fundamentals of oligonucleotide interactions, and to determine what factors control the shape, size, and internal structure of oligonucleotide-polyelectrolyte complex micelles.
|Advisor:||Tirrell, Matthew V.|
|Commitee:||Lee, Ka Yee C., Tian, Bozhi|
|School:||The University of Chicago|
|School Location:||United States -- Illinois|
|Source:||DAI-B 80/05(E), Dissertation Abstracts International|
|Subjects:||Chemistry, Physical chemistry|
|Keywords:||Micelles, Nucleic acids, Polyelectrolytes, Polymers, Scattering|
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