Advancing and expanding siRNA and saRNA therapeutics applications through chemical modifications
type: CreativeWork
description: Oligonucleotides are short strands of DNA or RNA that are used to treat complex diseases like cancer and rare genetic diseases. They rely on biological pathways in our body to work. Two pathways that are important to this study are gene silencing and activation. Short interfering RNAs (siRNAs) silence genes, while short activating RNAs (saRNAs) activate them. Both types of strands can be used to create new cancer treatments. However, RNA-based therapies face challenges like instability, off-target effects, and low cell membrane permeability. To overcome these challenges, this study focuses on incorporating new chemical modifications into the RNA and assessing their impact on RNA activity. Our aim is to enhance RNA therapeutic efficacy for potential cancer therapy applications. The first goal focused on creating a combination therapy for cancer treatment by directly conjugating free base corrole molecules to siRNA. This novel construct created a combination therapy effect of gene silencing and simultaneous photodynamic therapy (PDT). This combination therapy is expected to be more targeted and non-invasive compared to traditional cancer treatments like surgery or chemotherapy. The second goal of this research involved exploring the potential of metal corrole molecules within siRNA for personalized cancer treatment. In this study, Ga-corrole was directly conjugated to siRNA, resulting in an advanced treatment consisting of live imaging and gene silencing. This novel construct created a new tool for siRNA real-time imaging applications that could potentially allow for real-time drug monitoring during cancer treatment. The third goal focused on discovering nuclease-resistant and active saRNAs targeting STING, which is a potential target for the treatment of solid tumors. In this study, a library of chemically modified saRNA was screened for their nuclease resistance ability and investigated for any potential correlations between chemical modifications, nuclease resistan…
abstract: Oligonucleotides are short strands of DNA or RNA that are used to treat complex diseases like cancer and rare genetic diseases. They rely on biological pathways in our body to work. Two pathways that are important to this study are gene silencing and activation. Short interfering RNAs (siRNAs) silence genes, while short activating RNAs (saRNAs) activate them. Both types of strands can be used to create new cancer treatments. However, RNA-based therapies face challenges like instability, off-target effects, and low cell membrane permeability. To overcome these challenges, this study focuses on incorporating new chemical modifications into the RNA and assessing their impact on RNA activity. Our aim is to enhance RNA therapeutic efficacy for potential cancer therapy applications. The first goal focused on creating a combination therapy for cancer treatment by directly conjugating free base corrole molecules to siRNA. This novel construct created a combination therapy effect of gene silencing and simultaneous photodynamic therapy (PDT). This combination therapy is expected to be more targeted and non-invasive compared to traditional cancer treatments like surgery or chemotherapy. The second goal of this research involved exploring the potential of metal corrole molecules within siRNA for personalized cancer treatment. In this study, Ga-corrole was directly conjugated to siRNA, resulting in an advanced treatment consisting of live imaging and gene silencing. This novel construct created a new tool for siRNA real-time imaging applications that could potentially allow for real-time drug monitoring during cancer treatment. The third goal focused on discovering nuclease-resistant and active saRNAs targeting STING, which is a potential target for the treatment of solid tumors. In this study, a library of chemically modified saRNA was screened for their nuclease resistance ability and investigated for any potential correlations between chemical modifications, nuclease resistan…
author: Giorgees, Ifrodet
language: en
date published: 2024-04-01
date modified: 2026-07-24T05:35:20Z
provider: Ontario Institute of Technology
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Ontario Institute of Technology

PropertyValue
property ID: Handle
value: https://hdl.handle.net/10155/1781