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- W4237517049 abstract "Many forms of oligonucleotides, such as antisense DNA, small interfering RNA, and aptamers, have been investigated as therapeutic agents with moderate but growing commercial success. Natural, unmodified nucleic acids exhibit unfavorable biopharmaceutical characteristics that greatly limit their rate of clinical translation. The adoption of chemical modifications and/or carrier systems (typically polycationic) has led to significant improvements, but the field still faces challenges including toxicity, immunogenicity, and limited biodistribution to non-hepatic organs. In Chapters 2 and 3, we describe two carrier-free, stimuli-responsive, self-delivering nanostructure systems that can intracellularly co-deliver the drug and the DNA without a carrier. We demonstrate that the densely-functionalized DNA-drug nanostructures, which are formed through the self-assembly of DNA-drug amphiphiles, exhibit enhanced nuclease stability and cellular uptake, and the two payloads can be released in a controlled manner once a trigger (light or bioreduction) is applied. The exploration of these micellar DNA particles also led us to investigate better synthetic strategies to allow for manipulation of DNA in the organic phase. In Chapter 4, we describe a facile route to synthesize hydrophobic oligonucleotide precursors, which can be later converted to natural, hydrophilic DNA after manipulation in the organic phase. Using the ring-opening metathesis polymerization, we demonstrate that this strategy greatly expands the types of DNA-based nanostructures that are synthetically accessible. We anticipate that the marriage of oligonucleotides with the vast range of organic-phase polymerization techniques will result in many new classes of materials with yet unknown properties." @default.
- W4237517049 created "2022-05-12" @default.
- W4237517049 creator A5088292308 @default.
- W4237517049 date "2021-05-10" @default.
- W4237517049 modified "2023-10-18" @default.
- W4237517049 title "Novel oligonucleotide-polymer conjugates" @default.
- W4237517049 doi "https://doi.org/10.17760/d20316333" @default.
- W4237517049 hasPublicationYear "2021" @default.
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