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.
Results
Showing 1 to 20 of 922 for “"CRISPR"”.
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Extracellular Interaction Screening Using CRISPR Activation
… a cell-based genome-wide approach employing CRISPR activation to identify receptors for a defined ligand. We show receptors for high-affinity antibodies and low-affinity ligands can be unambiguously identified when used in pools or as individual binding probes. We apply this technique to …
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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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Modular CRISPR-diagnostics for Infectious Diseases
… (CARMEN and WATSON) that build on the existing CRISPR-diagnostic method SHERLOCK. SHERLOCK combines traditional amplification (PCR or isothermal) with target-specific CRISPR-Cas13 detection and enables new, modular assay designs. With CARMEN, we employ a droplet microfluidic platform to perform …
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Multiplexed Crispr Libraries For Cancer Functional Genomics
… with disease contexts. The adaptation of CRISPR/Cas9 has improved the sensitivity and specificity of functional screenings. Despite this advance, there remains a long-standing need to improve functional screenings with smaller and more versatile pooled libraries. Capitalizing on the …
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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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Quantitative modelling of CRISPR-Cas editing outcomes
Development of the CRISPR-Cas toolkit over the last decade has enabled unprecedented control over the genome and unlocked the capacity for new experiments and gene-therapies. However, use of these technologies is made more difficult due to variance in the rate and type of individual genetic …
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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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Resource competition in CRISPR-mediated gene regulation
CRISPR-mediated gene regulation is known for its ability to control multiple targets simultaneously due to its modular nature: the same dCas9 effector can target different genes simply by changing the associated gRNA. However, multiplexing requires the sharing of limited amounts of dCas9 protein …
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Anti-CRISPRs and CRISPR-Cas: Characterization and Biotechnology
… systems, and the more recently discovered CRISPR-Cas immune systems. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) loci together with their accompanying CRISPR-associated (Cas) genes form the only known bacterial adaptive defense mechanism that effectively protects …
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Targeting Duchenne muscular dystrophy with CRISPR base editors
Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2025-12-01
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Genetic correction of Parkinson’s disease using CRISPR-SKIP
… aggregation. We have recently demonstrated that CRISPR-Cas9 base editors can be used to induce exon skipping by mutating the conserved “AG” dinucleotide within the splice acceptor site preceding each exon. Here we demonstrate skipping of exon 3 in the SNCA gene in mammalian cells in culture by …
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CRISPR-mediated interrogation of small cell lung cancer
… and metastasis. The development of the CRISPR-Cas9 system has greatly facilitated genome editing in mammalian cells, leading to its widespread adoption for various applications in cancer biology. We have utilized this system in two complementary ways to investigate the molecular …
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Methods for CRISPR Cas12a Multiplexing in Mammalian Systems
… regularly interspaced short palindromic repeat (CRISPR) proteins have been found in many bacterial species, serving as a defense mechanism to defend the cell from bacteriophage invasion. These proteins are guided to cleave a specific nucleic acid sequence through the binding of a crRNA hairpin. …
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Precise and expansive genomic positioning for CRISPR edits
… of microbial adaptive immune systems, known as CRISPR, has enabled genome-wide engineering across all domains of life. A new generation of gene-editing tools has been fashioned from the natural DNA/RNA-targeting ability of certain CRISPR-associated (Cas) proteins and their guide RNA, which work …
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CRISPR Biosensors for Resource-limited Nucleic Acid Detection
… decision making. Recent advances in CRISPR-based biosensors has allowed for a new class of diagnostics with sequence-specific nucleic acid detection capabilities that can provide a rapid response without the need for traditional laboratory infrastructure. The research presented in …
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UNRAVELING TAZ REGULATION IN BREAST CANCER BY CRISPR SCREENING
… we conducted a series of loss-of-function CRISPR/Cas9 pooled genetic screens in vitro and in vivo on a selected subset of genes, previously identified in our laboratory as modulators of TAZ transcriptional activity. With this study we aimed to identify genes crucial for breast cancer cells …
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Bacterial defense islands: CRISPR-Cas and toxin-antitoxin systems /
… as restriction enzymes, bacterial argonautes and CRISPR-Cas systems. CRISPR-Cas systems are located in the genome part called “defense islands” where genes encoding different antiviral systems are clustered together. The goal of this thesis is to explore the mechanisms of action of type I …
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Identification and Characterization of Novel CRISPR-Cas Immune Effectors
… systems bacteria have evolved to combat this are CRISPR-Cas systems, which have been studied extensively due to their fascinating biology and usefulness in biotechnology and therapeutics. My thesis focuses on the discovery and characterization of three new CRISPR-Cas effector proteins that provide …
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Cas9-Primed Adaptive Immunity During the CRISPR-Cas Response
… regularly interspaced short palindromic repeats (CRISPR) loci provide archaea and bacteria with adaptive immune systems that allow them to counteract these rapidly evolving genetic parasites. These diverse systems all generally contain two components: a set of CRISPR-associated (cas) genes and a …
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CRISPR immune diversity in simulated and natural microbial populations
… impacts on the health of the human host. The CRISPR adaptive immune system is one of the ways in which microbes defend against viral infection, and it also holds a record of acquired immunity, allowing us to read a history of microbe-viral interactions. In this work, we examine the emergence, …
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