GENE-ENCODING DNA ORIGAMI AND BIOMOLECULAR CONDENSATES AS POTENTIAL DELIVERY PLATFORMS FOR NUCLEIC ACID THERAPEUTICS

Abstract

Nucleic acid therapeutics are extremely powerful biomedical technologies that have the potential to save millions of lives worldwide. However, at present, there are only about 37 nucleic acid therapeutics which are approved by the FDA, as compared to more than 10,000 approved pharmaco-chemical drugs, highlighting the immense potential to develop these therapeutics in terms of their application space and complexity. In order to enable the development of safer, more effective and longer-lasting nucleic acid therapeutics for genetic diseases, this dissertation establishes the use of a pure cell-free transcription-translation (TXTL) system for benchtop studies and uses this to evaluate the design and expression of gene-encoding DNA origami NPs (Chapter 3) and establishes the use of de novo peptide coacervates as a nucleic acid delivery platform that can protect gene templates (such as plasmids, linear DNA and DNA origami) against exogenous nuclease degradation (Chapter 4).