Date of Award

Spring 2026

Degree Type

Thesis

Department

Chemistry and Biochemistry

Director of Thesis

Nicholas Truex

Second Reader

Joanna Koryo Kwao

Abstract

Programming DNA-binding proteins is an effective strategy for developing therapeutics that regulate gene expression. These proteins can directly bind to DNA to activate or repress transcription of specific genes. Zinc finger proteins are a class of DNA-binding proteins commonly found in eukaryotic organisms. Their DNA-binding function is derived from unique amino acid sequences within each domain that recognizes specific nucleotides, allowing each finger to selectively recognize three DNA base pairs. Adjoining of multiple domains in tandem allows recognition of a specific DNA sequence. Artificial transcription factors can be made of multiple zinc finger domains arranged in tandem and engineered to regulate expression of specific genes by fusing them to transcriptional activator domains, but achieving selective DNA recognition and gene activation remains a major challenge. Incorporating nonnatural amino acids to increased backbone rigidity offers a strategy improve DNA-binding in gene targeted immunotherapies. This thesis leverages protein synthesis to introduce modified residues into the backbone of biologically relevant DNA-binding proteins.

First Page

1

Last Page

26

Rights

© 2026, Jasmine Glover, Emma Otey, Joanna K. Kwao, & Nicholas Truex

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