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Design, Synthesis, and Testing of Synthetic Vectors for siRNA Delivery

  • Author(s): Johnson, Mark Edward
  • Advisor(s): Guan, Zhibin
  • et al.

The delivery of nucleic acids, in particular small interfering RNA (siRNA), holds

great potential for research and therapeutic applications; however, the design of effective

delivery vectors remains a major challenge. In this dissertation, we have pursued a variety of strategies for the synthesis and discovery of vectors for the delivery of siRNA.

Chapter 1 provides a brief introduction to the applications of nucleic acid delivery

and the challenges involved in successfully siRNA to cellular targets both in vitro and in

vivo. Several previously developed vector systems which heavily influenced the design of the vectors discussed in this dissertation are discussed. Chapter 2 details the design and development of a dendritic peptide bolaamphiphile vector capable of efficient siRNA

delivery. Chapter 3 discusses attempts to modify and optimize the original bolaamphiphile system through co-formulation, synthesis of discrete variants, and alteration of the aromatic component. Chapter 4 discusses the design, synthesis, and testing of fluorocarbon modified polyethylenimine for the purpose of siRNA delivery. Chapter 5 explores the use of gold nanoparticles functionalized with dendritic amino acid based ligands, again for the delivery of siRNA.

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