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Development of Synthetic Materials for RNA Delivery


RNA-based therapeutics has garnered tremendous attention due to their potential to revolutionize vaccination, protein replacement therapies, and the treatment of genetic diseases. However, safe and efficient RNA delivery is still a critical challenge for widespread therapeutic applications. In this dissertation, we developed a variety of biodegradable molecular carriers for the delivery of various RNA, including siRNA, mRNA, and CRISPR-Cas9 machinery.

Chapter 1 provides a concise introduction to gene therapy and RNA therapy, along with critical challenges and strategies for developing RNA delivery vehicles. It also summarizes different categories of current RNA delivery materials and previous work completed in our lab.

Chapter 2 describes the design and development of a multivalent peptide-functionalized bioreducible polymer system for universal, safe, and efficient delivery of various RNAs of different lengths and structures. This work provides a novel promising vector system for universal RNA delivery, which may speed up the clinical application of RNA therapy and allow for the co-delivery of multiple RNAs.

Chapter 3 describes a series of peptide-functionalized bioreducible amphiphilic vectors for safe and efficient siRNA delivery. It also discusses the details of vector design and the correlations between chemical structures and biological functions.

Chapter 4 explores a family of poly(thymine) peptide nucleic acid-functionalized bioreducible polymers for mRNA delivery. This work provides a novel strategy for mRNA delivery by introducing hydrogen-binding into RNA-vector complexation.

In Chapter 5, I discussed another research project in my Ph.D. study, which is developing hybrid organic-inorganic quantum dot superlattices for next-generation photovoltaics. This work provides a hybrid quantum dot-molecular wire approach to construct highly-ordered nanocrystal films, which brings in significantly enhanced charge transport.

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