Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 572 for “"CRISPR/Cas9"”.
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Epigenetic Determinants of CRISPR-Cas9 genotoxicity
Gene editing therapies, such as those using CRISPR-Cas9, offer promising treatment options for genetic disorders. However, they also present unique safety assessment challenges including detection of off-target effects and unintended genomic alterations. An unresearched area of these concerns …
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Modulation of the CRISPR-Cas9 Immune Response
… immune systems to protect themselves, including CRISPR-Cas. CRISPR-Cas systems provide adaptive immunity through the acquisition of short DNA sequences from invading phages, known as spacers. Spacers are inserted into the CRISPR locus and serve as templates for the transcription of guides used by …
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Constructing and deconstructing cancer using CRISPR-Cas9
… first part of this thesis, I describe a novel CRISPR-Cas9-based approach for rapid functional investigation of candidate genes in vivo using well established autochthonous mouse models of cancer. By employing this platform in a GEMM of lung adenocarcinoma in vivo, I have functionally validated …
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Using CRISPR/Cas9 to modify the genome of cattle
… production. The gene editing technology CRISPR has expanded the possibilities of gene editing. The Cas9 nuclease creates a double strand break which can be repaired by non-homologous end joining (NHEJ) or homology directed repair (HDR). The goal of this experiment was to create a single …
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Focused CRISPR-Cas9 screens investigating the DNA damage response
… therapeutic opportunities. We demonstrate that CRISPR-Cas9 gene editing is a useful tool in genetic screens investigating the DDR. We present the results of three screens using focused CRISPR-Cas9 guide RNA libraries each interrogating different aspects of DDR biology. Firstly, we used a …
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Harnessing CRISPR-Cas9 screens to identify functional genetic interactions
The advent of CRISPR-Cas9 genetic engineering technologies has vastly improved our ability to interrogate genetic interactions in high-throughput studies. CRISPR-Cas9 screens have rapidly evolved to become the main approach for unbiased, genome-wide, forward genetic studies. This work seeks to …
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Genetic screens in vivo using the CRISPR/Cas9 system
An unmet and paramount need in the field of cancer research is to rapidly translate basic biological findings to clinically relevant therapeutics for cancer patients. Recent technological advances have generated many innovative applications to cancer biology and in a short time have yielded a …
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A novel CRISPR-Cas9 platform with divergent targeting capabilities
RNA-guided DNA endonucleases of the CRISPR-Cas system are widely used for genome engineering and thus have numerous applications in a wide variety of fields. The range of sequences that CRISPR endonucleases can recognize, however, is constrained by the need for a specific protospacer adjacent motif …
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CRISPR/Cas9-mediated ATG7 knockout results in enhanced osteosarcoma chemosensitivity
… common chemotherapy drugs. In the current study, CRISPR/Cas9 was used to knockout (KO) ATG7, a key gene in the autophagy process, in HOS-143B (highly metastatic/aggressive) osteosarcoma cells. Successful knockout of ATG7, and the autophagy process, was validated by qPCR and cell viability assays. …
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OPTIMISATION AND THERAPEUTIC-TARGET-DISCOVERY ORIENTED ANALYSIS OF CRISPR-CAS9 SCREENS
The emergence of CRISPR-Cas9 technology has revolutionized cancer research by enabling targeted genome modifications in tumour cells, offering insights into cancer biology and potential treatment targets. My PhD research focuses on developing tailored tools and pipelines to enhance the analysis of …
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Development of CRISPR/Cas9-based gene drive biotechnology in S. cerevisiae
… Saccharomyces cerevisiae as a model to develop CRISPR/Cas9-based gene drive biotechnology. The CRISPR/Cas9 biotechnology is a powerful gene editing tool used to modify target genomic sequences in all forms of living creatures including animals, plants, fungi, and bacteria. One potential …
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Biases and Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens
<p>Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. …
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Generation of Memory of Infection During the CRISPR-Cas9 Immune Response
… regularly interspaced short palindromic repeat (CRISPR) loci and their associated (Cas) proteins provide adaptive immunity against viral attack in prokaryotes. Upon infection, short phage sequences known as spacers integrate between CRISPR repeats and are transcribed into small RNA molecules that …
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Investigating the role of chromatin modifications in CRISPR/Cas9 gene editing
… and heterochromatin have been shown to impede CRISPR/Cas9 editing efficiency. Conversely, Cas9 can open previously inaccessible regions of DNA, and transcriptionally silent targets can usually be edited without difficulty. In order to address this paradox, we have developed a method that …
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Identification of novel synthetic lethal interactions using multiplexed CRISPR-Cas9 screening
… interactions and built a bespoke multiplex CRISPR-Cas9 library to interrogate 1192 gene-pair interactions. We deployed this library on a panel of melanoma cell lines and a retinal pigment epithelial cell line as a normal comparator. We went on to develop a bioinformatic pipeline with which …
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Genomewide Crispr/Cas9 Screen Identifies Network of Protein Complexes That Regulate Trim24
… this possibility, I performed a genomewide CRISPR/Cas9 screen library using fluorescence activated cell sorting (FACS) to identify regulators of TRIM24. The screen was enabled by two innovations. I engineered cells with an in-frame knock-in of mClover3 to the endogenous copy of TRIM24 to …
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Better safe than sorry: new CRISPR/Cas9 tools for improved genome engineering
CRISPR nucleases are efficient tools to edit cellular genomes in a variety of organisms. However, the in vivo application of this technology is still severely limited by unwanted genomic cleavages, that are further increased by long-term expression of the nuclease and can lead to unpredictable …
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Genome editing with CRISPR-Cas9 in the Illinois long term selection experiment
… Regularly Interspaced Palindromic Repeat (CRISPR) and CRISPR Associated Protein 9 (Cas9) have markedly increased our ability to characterize genes and use genetics to the benefit of agriculture. In this work, we utilize this technology to study the Illinois Long Term Selection Experiment …
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