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Description
The effects of specific histone deacetylase inhibitors (HDACi) on transgene expression in combination with a novel polymer as a delivery vehicle are investigated in this research. Polymer vectors, although safer than viruses, are notorious for low levels of gene expression. In this investigation, the use of an emerging chemotherapeutic anti-cancer

The effects of specific histone deacetylase inhibitors (HDACi) on transgene expression in combination with a novel polymer as a delivery vehicle are investigated in this research. Polymer vectors, although safer than viruses, are notorious for low levels of gene expression. In this investigation, the use of an emerging chemotherapeutic anti-cancer drug molecule, HDACi, was used to enhance the polymer-mediated gene expression. HDACi are capable of inhibiting deacetylation activities of histones and other non-histone proteins in the cytoplasm and nucleus, as well as increase transcriptional activities necessary for gene expression. In a prior study, a parallel synthesis and screening of polymers yielded a lead cationic polymer with high DNA-binding properties, and even more attractive, high transgene expressions. Previous studies showed the use of this polymer in conjunction with cytoplasmic HDACi significantly enhanced gene expression in PC3-PSMA prostate cancer cells. This led to the basis for the investigation presented in this thesis, but to use nuclear HDACi to potentially achieve similar results. The HDACi, HDACi_A, was a previously discovered lead drug that had potential to significantly enhance luciferase expression in PC3-PSMA cells. The results of this study found that the 20:1 polymer:plasmid DNA weight ratio was effective with 1 uM and 2 uM HDACI_A concentrations, showing up to a 9-fold enhancement. This enhancement suggested that HDACi_A was effectively aiding transfection. While not an astounding enhancement, it is still interesting enough to investigate further. Cell viabilities need to be determined to supplement the results.
ContributorsLehrman, Jennifer (Author) / Rege, Kaushal (Thesis advisor) / Caplan, Michael (Committee member) / Pizziconi, Vincent (Committee member) / Arizona State University (Publisher)
Created2012
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Description

Y-chromosomes exist in the body cells of many kinds of male animals. Found in the nucleus of most living animal cells, the X and Y-chromosomes are condensed structures made of DNA wrapped around proteins called histones. The individual histones bunch into groups that the coiled DNA wraps around called a

Y-chromosomes exist in the body cells of many kinds of male animals. Found in the nucleus of most living animal cells, the X and Y-chromosomes are condensed structures made of DNA wrapped around proteins called histones. The individual histones bunch into groups that the coiled DNA wraps around called a nucleosome, which are roughly 10 nano-meters (nm) across. The histones bunch together to form a helical fiber (30 nm) that spins into a supercoil (200 nm). During much of a cell's life, DNA exists in the 200 nm supercoil phase. But when DNA replicates itself, supercoils condense further into visible chromosomes with diameters of about 1400 nm. The X- and Y-chromosomes carry the genetic information that determines the sex of many types of animals. The Y-chromosome contains a gene called the sex-determining region Y, or the SRY gene in humans. If a fertilized egg, called a zygote, has the SRY gene, the zygote develops normally into an adult organism with male sex traits. Zygotes without the SRY gene develop to have female traits. Zygotes with Y-chromosomes but mutated SRY genes can develop into adult organisms that have female traits.

Created2017-02-06