Дисертації з теми "Gene Editing (CRISPR/Cas9)"
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Roidos, Paris. "Genome editing with the CRISPR Cas9 system." Thesis, KTH, Skolan för bioteknologi (BIO), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-163694.
Sousa, Maria Cristina Ferreira de. "Targeted gene editing in Neospora caninum using CRISPR/Cas9." Master's thesis, Universidade de Évora, 2021. http://hdl.handle.net/10174/29205.
Cui, Xiucheng. "Targeted Gene Editing Using CRISPR/Cas9 in a Wheat Protoplast System." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36543.
Croci, Susanna. "CRISPR-Cas9 gene editing: a new promising treatment for Rett syndrome." Doctoral thesis, Università di Siena, 2020. http://hdl.handle.net/11365/1120546.
Cullot, Grégoire. "Génotoxicité des systèmes CRISPR-Cas9." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0344.
Gene therapy is a promising therapeutic strategy for the monogenic diseases treatment. If the first approaches, called additive, have relied on the use of viral vectors, a growing share is now turning to gene editing. Less than a decade after its characterization, the CRISPR-Cas9 system has moved gene editing to a clinical stage. However, in the same period of time, several questions have been raised regarding the genotoxicity that can be induced by Cas9. An emerging literature points to the risk of genotoxicity at the targeted site. The thesis work presented here is part of this theme. The first part of the study aimed to describe the genotoxicity induced by a single double-stranded break made by Cas9. Characterization of the effects was done both at the nucleotide level, by monitoring the HDR / InDels balance, but also at the chromosome scale. The monitoring of chromosomal integrity has brought to light a new risk of genotoxicity that was not characterized. A sensitive and specific detection system for this risk has been developed to further characterize it. The second objective was to address the limitations of unwanted genotoxicity by developing a safer and more efficient gene editing method through the use of a single single-stranded breakage by Cas9D10A-nickase
Giada, Beligni. "Application of the CRISPR-Cas9 genome editing approach for the correction of the p.Gly2019Ser (c.6055G>A) LRRK2 variant in Parkinson Disease." Doctoral thesis, Università di Siena, 2022. https://hdl.handle.net/11365/1220257.
Poggi, Lucie. "Gene editing approaches of microsatellite disorders : shortening expanded repeats." Electronic Thesis or Diss., Sorbonne université, 2020. http://www.theses.fr/2020SORUS412.
Microsatellite disorders are a specific class of human diseases that are due to the expansion of repeated sequences above pathological thresholds. These disorders have varying symptoms and pathogenic mechanisms, caused by the expanded repeat. No cure exists for any of these dramatic conditions. This thesis is investigating new gene editing approaches to remove pathological expansions in the human genome. In a first part, a yeast-based screen was constructed to identify potent CRISPR-associated nucleases that can cut these microsatellites. The second part focuses on myotonic dystrophy type 1 (DM1), which is due to and expanded CTG repeat tract located at the 3’UTR of the DMKP gene. A nuclease, TALENCTG was designed to induce a double strand break into the CTG repeats. It was previously shown to be active in yeast cells, inducing contractions of CTG repeats from a DM1 patient integrated into the yeast genome. The TALEN was tested in DM1 patient cells. The nuclease was found to trigger some contraction events in patient cells. In vivo experiments were carried out in a mouse model of myotonic dystrophy type 1 containing a human genomic fragment from a patient and 1000 CTG. Intramuscular injections of recombinant AAV encoding the TALENCTG revealed that the nuclease is toxic and/or immunogenic in muscle cells in the tested experimental conditions. Finally, the reporter assay integrated in yeast to screen nucleases was transposed in HEK293FS cell line. The integrated cassette contains a CTG expansion from a myotonic dystrophy type 1 patient flanked by two halves of GFP genes. This system would enable to find nucleases active in human cells
Waghulde, Harshal B. "Mapping and CRISPR/Cas9 Gene Editing for Identifying Novel Genomic Factors Influencing Blood Pressure." University of Toledo Health Science Campus / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=mco1470402637.
Jayavaradhan, Rajeswari. "Optimization of Gene Editing Approaches for Human Hematopoietic Stem Cells." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1543919940219677.
Ryu, Junghyun. "The direct injection of CRISPR/Cas9 system into porcine zygotes for genetically modified pig production." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/101763.
Doctor of Philosophy
Amaya, Colina Anais Karime. "Towards the Treatment of Human Genetic Liver Disease by AAV-Mediated Genome Editing and Selective Expansion of Repaired Hepatocytes." Thesis, The University of Sydney, 2019. https://hdl.handle.net/2123/21893.
Campbell, Ian. "Optimization of Methods for Generating Customized Gene-Edited Human Pluripotent Stem Cells." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1504802720510926.
Feehan, Joanna Marie. "Development of methodology for genome editing in Xenopus laevis using CRISPR/Cas9, targeting the rhodopsin gene." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/57863.
Medicine, Faculty of
Graduate
Hsu, Patrick David. "Development of the CRISPR nuclease Cas9 for high precision mammalian genome engineering." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:13068392.
Murakami, Yu. "Establishment of a practical gene knock-in system and its application in medaka." Kyoto University, 2020. http://hdl.handle.net/2433/253339.
0048
新制・課程博士
博士(農学)
甲第22503号
農博第2407号
新制||農||1077(附属図書館)
学位論文||R2||N5283(農学部図書室)
京都大学大学院農学研究科応用生物科学専攻
(主査)教授 佐藤 健司, 教授 澤山 茂樹, 准教授 豊原 治彦
学位規則第4条第1項該当
Bella, R. "GENE EDITING TECHNOLOGIES BASED ON CRISPR-CAS9 SYSTEM FOR THE TREATMENT OF HIV: STUDIES IN VITRO AND IN VIVO." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/543298.
Corrado, A. "Evaluation of gene editing strategies based on CRISPR/Cas9 to study specific alleles of LGALS3 associated with the risk of papillary thyroid carcinoma." Doctoral thesis, Università di Siena, 2018. http://hdl.handle.net/11365/1040553.
Prescott, Jack. "Interrogating novel functions of the I kappa B kinases via CRISPR-Cas9 gene editing and small molecule inhibition." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/277025.
Fine, Eli Jacob. "A toolkit for analysis of gene editing and off-target effects of engineered nucleases." Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/54875.
Haward, Fiona. "Investigation of the physiological roles of SRSF1-mediated translation." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31188.
Stens, Cassandra, Isabella Enoksson, and Sara Berggren. "The CRISPR-Cas system." Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-171997.
BONOMELLI, SARA. "L'EDITING GENETICO GERMINALE UMANO, TRA PROBLEMI ETICI E QUESTIONI DI GOVERNANCE." Doctoral thesis, Università degli Studi di Milano, 2022. http://hdl.handle.net/2434/922688.
Souza, Gustavo Torres de. "Produção de células MDBK expressando a enzima CAS9 e edição do gene da beta-lactoglobulina pelo sistema CRISPR/Cas9." Universidade Federal de Juiz de Fora (UFJF), 2017. https://repositorio.ufjf.br/jspui/handle/ufjf/6049.
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CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
O advento sistema CRISPR/Cas9 tornou o processo de edição gênica consideravelmente mais fácil e direto, uma vez que retirou empecilhos técnicos relacionados aos sistemas já disponíveis. Desta forma, foram permitidos diversos avanços no entendimento da função de elementos genômicos, assim como a produção de embriões geneticamente modificados com diversas finalidades. O atual trabalho objetivou a edição gênica no gene da beta-lactoglobulina em células somáticas bovinas objetivando a produção futura de embriões da espécie geneticamente modificados. Considerando-se que a hipersensibilidade a essa proteína responde pela maior parte das alergias ao leite bovino, a produção de animais cujo leite não contenha essa molécula é de grande interesse para a indústria de laticínios. Durante os experimentos, foi possível obter uma linhagem de células bovinas MDBK expressando a enzima Cas9 (MDBK-Cas). Usando células MDBK e as células MBDK-Cas foi possível se obter com sucesso edições gênicas no locus beta-lactoglobulina utilizando-se os componentes do sistema CRISPR/Cas9 na forma de mRNA da proteína Cas9 e sgRNAs. Conclui-se que o sistema CRISPR/Cas9 pode ser usado com os sgRNA desenhados neste estudo para editar o gene da betalactoglobulina em células MDBK. Assim, células MDBK podem ser utilizadas como alvo o locus em estudo. Modelos de estudos para edição do genoma bovino. Em vista da escassa literatura constando de trabalhos em que tenha sido feita a edição gênica em embriões bovinos, os dados gerados por esse trabalho colaborarão para o avanço do estado da arte no que diz respeito a engenharia gênica de bovinos e no conhecimento do funcionamento do sistema CRISPR/Cas9.
The advent of the CRISPR / Cas9 system made the process of gene editing considerably easier and more straightforward, since it removed technical impediments related to the systems already available. In this way, several advances were made in the understanding of the function of genomic elements, as well as the production of genetically modified embryos for various purposes. The present work aimed at the genetic editing of the beta-lactoglobulin gene in bovine somatic cells aiming at the future production of genetically modified embryos of the species. Considering that hypersensitivity to this protein accounts for most of the allergies to bovine milk, the production of animals whose milk does not contain this molecule is of great interest to the dairy industry. During the experiments, it was possible to obtain a lineage of bovine MDBK cells expressing the Cas9 enzyme (MDBK-Cas). Using MDBK cells and MBDKCas cells it was possible to successfully obtain gene editions at the beta-lactoglobulin locus using the components of the CRISPR / Cas9 system as mRNA of the Cas9 protein and sgRNAs. It is concluded that the CRISPR / Cas9 system can be used with the sgRNAs designed in this study to edit the beta-lactoglobulin gene in MDBK cells. Thus, MDBK cells can be targeted as the locus under study. Models of studies for editing the bovine genome. In view of the scarce literature consisting of studies in which bovine embryos have been genetically engineered, the data generated by this work will contribute to the advancement of the state of the art regarding the genetic engineering of cattle and the knowledge of the functioning of the system CRISPR / Cas9.
Nejat, Naghmeh. "Gene editing of the representative WRKY family members in an elite malting barley cultivar RGT Planet by CRISPR/Cas9." Thesis, Nejat, Naghmeh (2022) Gene editing of the representative WRKY family members in an elite malting barley cultivar RGT Planet by CRISPR/Cas9. PhD thesis, Murdoch University, 2022. https://researchrepository.murdoch.edu.au/id/eprint/66511/.
Foster, Robert Graham. "Development of a modular in vivo reporter system for CRISPR-mediated genome editing and its therapeutic applications for rare genetic respiratory diseases." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/33040.
Xu, Huaigeng. "Targeted Disruption of HLA genes via CRISPR-Cas9 generates iPSCs with Enhanced Immune Compatibility." Kyoto University, 2019. http://hdl.handle.net/2433/242420.
Schneider, Sara Jane. "Delivery of CRISPR/Cas9 RNAs into Blood Cells of Zebrafish: Potential for Genome Editing in Somatic Cells." Thesis, University of North Texas, 2017. https://digital.library.unt.edu/ark:/67531/metadc1011754/.
BORRELLI, VIRGINIA MARIA GRAZIA. "Caratterizzazione del gene LIPOSSIGENASI 4 e approccio CRISPR-Cas9 per aumentare la resistenza alla fusariosi di mais." Doctoral thesis, Università Cattolica del Sacro Cuore, 2018. http://hdl.handle.net/10280/53792.
Fusarium verticillioides (Fv) causes ear rot in maize and contaminates the kernels with fumonisins, a family of mycotoxins that affects feed and food and considered carcinogenic for humans and animals. Several studies were conducted to identify maize genes associated with host plant resistance to Fv infection and fumonisin accumulation. It is known that plant lipoxygenase (LOX)-derived oxylipins regulate defense against pathogens and that the host-pathogen lipid cross-talk influences the pathogenesis. In this regard, maize mutants carrying Mu insertions in the ZmLOX4 gene, the susceptible W22 and the resistant TZI18 lines were tested for Fv resistance by the screening method rolled towel assay (RTA). Additionally, the expression profiles of 16 genes involved in the LOX and green leaves volatiles (GLV) pathway were studied and the lipoxygenase activity was investigated in the same lines as well. Furthermore, the genome editing technology of Clustered Regularly Interspaced Short Palindromic Repeat/associated Cas9 (CRISPR/Cas9) was applied in order to investigate the possible implication of the lipoxygenase gene ZmLOX6 and the transcription factor ZmWRKY125 in the resistance mechanisms against Fv. The enhanced expression of these genes was previously observed by RNA - Seq experiments in maize resistant genotypes and Genome Wide Association Studies (GWAS) resulted in one SNP significantly associated with ZmWRKY125. Moreover, the gene ZmLOX4 was over-expressed in the line A188 for evaluating a possible improvement of the disease resistance towards Fv. The CRISPR cloning was based on a double cloning using two different guides (sgRNA) for one gene target. The constructs under the maize promoter ZmpUBI in the binary vector p1609 were transformed into the maize A188 line using Agrobacterium tumefaciens mediated transformation. Maize plants edited in the genes ZmLOX6 and ZmWRKY125, and over-expressing ZmLOX4 will be characterized for Fv resistance using rolled towel assay, field assay and for their fumonisin content. Furthermore, the content of jasmonic acid, its derivative metabolites, and oxylipins will be tested, as well as the expression analysis of the main genes involved in the jasmonic acid pathway will be performed.
BORRELLI, VIRGINIA MARIA GRAZIA. "Caratterizzazione del gene LIPOSSIGENASI 4 e approccio CRISPR-Cas9 per aumentare la resistenza alla fusariosi di mais." Doctoral thesis, Università Cattolica del Sacro Cuore, 2018. http://hdl.handle.net/10280/53792.
Fusarium verticillioides (Fv) causes ear rot in maize and contaminates the kernels with fumonisins, a family of mycotoxins that affects feed and food and considered carcinogenic for humans and animals. Several studies were conducted to identify maize genes associated with host plant resistance to Fv infection and fumonisin accumulation. It is known that plant lipoxygenase (LOX)-derived oxylipins regulate defense against pathogens and that the host-pathogen lipid cross-talk influences the pathogenesis. In this regard, maize mutants carrying Mu insertions in the ZmLOX4 gene, the susceptible W22 and the resistant TZI18 lines were tested for Fv resistance by the screening method rolled towel assay (RTA). Additionally, the expression profiles of 16 genes involved in the LOX and green leaves volatiles (GLV) pathway were studied and the lipoxygenase activity was investigated in the same lines as well. Furthermore, the genome editing technology of Clustered Regularly Interspaced Short Palindromic Repeat/associated Cas9 (CRISPR/Cas9) was applied in order to investigate the possible implication of the lipoxygenase gene ZmLOX6 and the transcription factor ZmWRKY125 in the resistance mechanisms against Fv. The enhanced expression of these genes was previously observed by RNA - Seq experiments in maize resistant genotypes and Genome Wide Association Studies (GWAS) resulted in one SNP significantly associated with ZmWRKY125. Moreover, the gene ZmLOX4 was over-expressed in the line A188 for evaluating a possible improvement of the disease resistance towards Fv. The CRISPR cloning was based on a double cloning using two different guides (sgRNA) for one gene target. The constructs under the maize promoter ZmpUBI in the binary vector p1609 were transformed into the maize A188 line using Agrobacterium tumefaciens mediated transformation. Maize plants edited in the genes ZmLOX6 and ZmWRKY125, and over-expressing ZmLOX4 will be characterized for Fv resistance using rolled towel assay, field assay and for their fumonisin content. Furthermore, the content of jasmonic acid, its derivative metabolites, and oxylipins will be tested, as well as the expression analysis of the main genes involved in the jasmonic acid pathway will be performed.
MINGOIA, MAURA. "Terapia genica della β Talassemia mediante editing del DNA". Doctoral thesis, Università degli Studi di Cagliari, 2016. http://hdl.handle.net/11584/266632.
Kennedy, Zachary C. "Optimizing CRISPR/Cas9 for Gene Silencing of SOD1 in Mouse Models of ALS." eScholarship@UMMS, 2019. https://escholarship.umassmed.edu/gsbs_diss/1047.
Kelterborn, Simon. "Gen-Editierung von Photorezeptorgenen in der Grünalge Chlamydomonas reinhardtii mithilfe des CRISPR/Cas9-Systems." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/21903.
Gene editing is a fundamental tool in molecular biosciences in order to study the function of genes (reverse genetics). This study established zinc-finger and CRISPR/Cas9 nucleases for gene editing to target and inactivate the photoreceptor genes in C. reinhardtii. In continuation of previous work with designer zinc-finger nucleases (ZFN), the transformation efficiency could be improved 300-fold, which enabled the inactivation of genes in motile wild type cells. This made it possible to disrupt the Channelrhodopsin-1 (ChR1), Channelrhodopsin-2 (ChR2) and Chlamyopsin-1/2 (COP1/2) genes individually and in parallel. Phototaxis experiments in these strains revealed that the inactivation of ChR1 had a greater effect on phototaxis than the inactivation of ChR2. To apply the CRISPR/Cas9 system, the transformation conditions were adapted and optimized so that the Cas9-gRNA complex was successfully electroporated into the cells as an in vitro synthesized ribonucleoprotein. This approach enabled gene inactivations with CRISPR/Cas9 in C. reinhardtii. In order to measure and improve the conditions for precise gene modifications, the SNRK2.2 gene was established as a reporter gene for a ‘Blue-Green test’. Small insertions of up to 30 bp were inserted using short oligonucleotides, while larger reporter genes (mVenus, SNAP-tag) were integrated using donor plasmids. Throughout this study, more than 20 non-selectable genes were disrupted, including 10 of the photoreceptor genes, with an average mutation rate of 12,1 %. Overall, this work shows in a comprehensive way how gene inactivations and modifications can be performed in green alga C. reinhardtii using ZFNs or CRISPR/Cas9. In addition, the collection of the ten photoreceptor knockouts provides a promising source to investigate the diversity of photoreceptor genes in C. reinhardtii.
Zhang, Yuan. "Functional Characterization of Beta-Glucuronosyltransferases (GLCATs) and Hydroxyproline-Galactosyltransferases (GALTs) Involved in Arabinogalactan-Protein (AGP) Glycosylation Using CRISPR/Cas9 Gene Editing Technology In Arabidopsis." Ohio University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1588687871450172.
Martínez, Fernández Carmen 1993. "C elegans and CRISPR/Cas gene editing to study BAP1 cancer-related mutations and cisplatin chemoresistance." Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2021. http://hdl.handle.net/10803/671159.
Los organismos modelo y las estrategias de edición genética son fundamentales para desentrañar incógnitas en ciencias de la vida, desde la investigación básica hasta investigación aplicada a la biomedicina. En este estudio, reafirmamos la importancia del uso de dos potentes herramientas, el sistema experimental Caenorhabditis elegans y la tecnología de edición genética CRISPR/Cas, para modelar mutaciones relacionadas con cáncer e investigar la quimiorresistencia al cisplatino. Hemos modelado mutaciones asociadas al síndrome de predisposición tumoral BAP1, en ubh-4/BAP1. Explorando el efecto de distintos alelos mutantes de ubh-4, hemos descubierto una interacción sintética entre ubh-4 y rpn-9, el cual codifica para una subunidad reguladora esencial para el ensamblaje del proteasoma. Además, proponemos que la cooperación funcional de dichos genes está implicada en la degradación de proteínas mediada por el sistema ubiquitina-proteasoma durante la profase meiótica. También hemos investigado la respuesta generada por la terapia con cisplatino en C. elegans. Por una parte, hemos demostrado que la toxicidad inducida por el cisplatino puede modularse alterando el metabolismo glucídico y lipídico. Por otro lado, hemos observado que esta droga genera disfunción mitocondrial. Finalmente, mediante un sistema automatizado, hemos puesto a punto un método para evaluar el efecto neurotóxico del cisplatino en el nemátodo y hemos encontrado que la dopamina posee un efecto protector.
Hamouri, Fatima. "Contrôle optique de l'activité de protéines et de l'expression de gènes, par photo-activation du cyclofène cagé, pour l’étude de l’initiation du cancer." Electronic Thesis or Diss., Sorbonne université, 2020. http://www.theses.fr/2020SORUS235.
The zebrafish has become an increasingly popular and valuable cancer model over the past decades. While most of these models are generated by expressing mammalian oncogenes under tissue-specific promoters, here we describe a method that allows for the precise optical control of oncogene expression or inactivation in live zebrafish. Thus, this technique allows for the induction of tumor phenotypes by activating the constitutive expression of a typical human oncogene, KRASG12V, in selected tissues and single cells without tissue-specific promoters in live zebrafish. We also demonstrate the optical control of oncogene expression as KRASG12V, CMYC and BRAFV600E as well as the control of the expression and the activity of the CRISPR-Cas9 system. In addition, it should be noted that accurate manipulation of gene expression is essential to understand most biological processes. Therefore, our work presents a novel approach to initiate and study cancer in zebrafish. Finally, it is also worth noting that the high spatio-temporal resolution of this method makes it a valuable tool for studying cancer initiation from single cells
Hahn, Florian [Verfasser], Andreas P. M. [Gutachter] Weber, and Peter [Gutachter] Westhoff. "Genome editing and establishment of efficient gene targeting approaches in Arabidopsis using the CRISPR/Cas9 system / Florian Hahn ; Gutachter: Andreas P. M. Weber, Peter Westhoff." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2018. http://d-nb.info/1159373612/34.
Sürün, Duran [Verfasser], Beatrix [Akademischer Betreuer] Süß, M. Cristina [Akademischer Betreuer] Cardoso, and Harald von [Akademischer Betreuer] Melchner. "High Efficiency Gene Correction in Hematopoietic Cells by Donor Template-free CRISPR/Cas9 Genome Editing / Duran Sürün ; Beatrix Süß, M. Cristina Cardoso, Harald von Melchner." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2018. http://d-nb.info/1153546396/34.
Yang, Luhan. "Development of Human Genome Editing Tools for the Study of Genetic Variations and Gene Therapies." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11117.
Ibraheim, Raed R. "Genome Engineering Goes Viral: Repurposing of Adeno-associated Viral Vectors for CRISPR-mediated in Vivo Genome Engineering." eScholarship@UMMS, 2020. https://escholarship.umassmed.edu/gsbs_diss/1114.
De, Santis Flavia. "Genome editing to understand neural circuits formation : a novel CRISPR/Cas9-based strategy for conditional mutagenesis and functional study of the role of the meteorin gene family in zebrafish neurodevelopment." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066269/document.
In recent years, the zebrafish (Danio rerio) has emerged as a powerful model organism to study neuronal circuit development and function. To date, different genome editing technologies allow the generation of constitutive mutant alleles, permitting the study of gene loss-of-function in this vertebrate model. Nevertheless, to assess the role of certain loci it might be required a precise spatiotemporal control of gene inactivation. The rst part of my thesis describes a novel strategy for tissue-specific gene disruption based on the CRISPR/Cas9 and the Gal4/UAS systems. The described technique allows the induction of somatic mutations in genetically labeled tissues, cell clones or single cells, making it possible to follow the effect of gene disruption in vivo via reporter gene expression. The second part of the thesis focuses on the functional analysis of the role of the meteorin gene family during neuronal development and axonal targeting in zebra sh. Meteorin family is conserved among vertebrates and its members have been shown to be involved in neuronal progenitor proliferation and differentiation and axonal elongation, in vitro. We used the zebrafish nervous system as a model to dissect the role of Meteorins during embryonic development, focusing on their potential role as novel guidance molecules. Interestingly, we found that genes belonging to the meteorin family are expressed along the midline of the larval central nervous system and at the floor plate in the hindbrain and spinal cord. We generated CRISPR/Cas9 mutant lines carrying out-of-frame deletions in the coding sequence of each member of the zebrafish meteorin family and we performed a comprehensive analysis of the establishment of axonal projections in the mutants. Our data pointed out that metrns loss-of-function affects the earliest process of axonal development, demonstrating a crucial role in the process of axonal outgrowth for this new family of evolutionary conserved guidance molecules
Raper, Austin T. "Mechanistic Studies of DNA Replication, Lesion Bypass, and Editing." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1529576739391675.
MERCURI, ELISABETTA. "PRECLINICAL MODELING HIGHLIGHTS THE THERAPEUTIC POTENTIAL OF THE ADOPTIVE TRANSPLANT OF GENE CORRECTED T CELLS IN X-LINKED HYPER-IGM IMMUNODEFICIENCY." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2020. http://hdl.handle.net/10281/263922.
Background The X-linked hyper-IgM syndrome type I (HIGM1) is caused by inactivating mutations in the CD40 ligand gene (CD40LG) that disrupt the T cell helper function on B cells and macrophages. This disease represents an ideal candidate for a gene correction strategy because preclinical studies of Hematopoietic Stem Cell (HSC) gene therapy have already shown i) evidence of potential efficacy even with few amounts of transduced cells; ii) critical safety issues due to unregulated transgene expression. Since in HIGM1 the genetic defect is not lethal to T cells, we aim to apply our gene editing strategy on autologous T cells that could be used to provide immediate therapeutic benefit to the patients by resolving pre-existing infections prior to a definitive HSPC transplant. Methods To establish which are the therapeutic threshold levels and transplant conditions required to achieve immune reconstitution and functional immunologic restoration with corrected cells, we infused different doses of WT T cells into HIGM1 mice pre-conditioned or not with different lymphodepleting regimens and performed competitive transplants of WT and Cd40lg-/- HSPC in the mouse model. Results While longitudinal blood analyses showed a long-term, stable T cell engraftment in all the conditions, highest engraftment rates were obtained in mice transplanted after chemotherapy treatment with cyclophosphamide (CPA). All the transplanted mice showed a partial rescue of the antigen-specific IgG response after immunization with Keyhole Limpet Hemocyanin (TNP-KLH) but a higher rescue was observed in mice pre-conditioned with CPA. These mice also showed the presence of TNP-KLH specific IgG producing B cells and germinal centers within splenic lymphoid follicles. HIGM1 mice reconstituted with increasing proportions of WT HSPC displayed a dose-dependent rescue of the T cell mediated immune response. In particular we found that 10% of WT HSPC is sufficient to partially restore serologic immunity against different antigens as well as to attenuate infection in HIGM1 mice challenged with Pneumocystis murina. Conclusions Our current efforts are aimed to demonstrate functional restoration of the immune response against Pneumocystis murina infection in HIGM1 mice that received adoptive transfer of WT CD4+ T cells. If successful, our findings will be instrumental to establish the therapeutic potential of a T cell gene correction approach for the treatment of the HIGM1 disease that could act as a bridge therapy to the HSPC-based strategy.
Moore, Janelle. "Establishment of CRISPR/Cas-9 Aided Knockout of the ZIC2 Gene in the African-American Prostate Cancer Cell Line E006AA-PR." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2019. http://digitalcommons.auctr.edu/cauetds/195.
Stephenson, Anthony Aaron. "Mechanistic studies of enzymes involved in DNA transactions." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1531497128385619.
Martineau, Sabrina. "Etude des mécanismes moléculaires de l'épidermolyse bulleuse simple à partir de cellules souches humaines induites à la pluripotence." Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASQ020.
Epidermolysis bullosa simplex (EBS) is a skin disorder caused mainly by dominant mutations in genes coding for keratin 5 (KRT5) or 14 (KRT14) genes. It is characterized by the presence of blisters caused by epidermal detachment, and by other complications such as cutaneous inflammation. From a genetic point of view, the mutations will alter the assembly of the keratin intermediate filament network in basal keratinocytes of the epidermis, leading to cell cytolysis and the formation of intra-epidermal blisters. Currently no effective therapeutic approach it is available. Understanding of the disease and the development of therapies have been hampered by the lack and limitations of relevant human cell and mouse models.So, the general aim of my thesis was to exploit the properties of human induced pluripotent stem cells (hiPSc) to modelling EBS. For this purpose, we generate hiPSc-derived keratinocytes from EBS patients carrying KRT5 mutations (Ker-EBS), and from healthy patients (Ker-WT). Comparison of Ker-EBS and Ker-WT enabled to show that Ker-EBS recapitulates the main phenotypes associated with EBS, namely decreased cell proliferation, increased cell migration, altered signalling pathways (ERK and JNK), as well as aggregates of intermediate keratin filaments in the cytoplasm, as observed in primary EBS keratinocytes. These results demonstrate that our hiPSc-derived cell model is relevant for study EBS.In order to identify new molecular mechanisms, a trancriptomic analysis comparing Ker-EBS with Ker-WT revealed 138 deregulated genes, revealing an enrichment in processes linked to the extracellular matrix, DNA packaging and the inflammatory response. As the inflammatory component in EBS has been poorly described, my next step was to study the pro-inflammatory cytokine phenotype. Thus, we were able to demonstrate increased expression of IL-1α, IL-1β, IL-6, IL-8 (CXCL8), CXCL5, CXCL10, CXCL11, CCL5 in Ker-EBS, at RNA level under basal or IFNy-stimulated conditions to mimic a pro-inflammatory context. Only the chemokines CXCL10 and CXCL11 are secreted at high concentrations in the culture supernatants of stimulated and unstimulated Ker-EBS, demonstrating the involvement of these cytokines in EBS.In parallel, in order to avoid biases due to genetic background, gender, patient age and epigenetics, we generated an isogenic Ker-EBS line (corrected Ker-EBS) using the CRISPR-Cas9 technique. We were thus able to demonstrate that the corrected Ker-EBS line showed a restoration of the expression level of the pro-inflammatory cytokines mentioned above, to a level close to that of Ker-WT, confirming a direct link between mutations in the KRT5 gene and the pro-inflammatory signature.In conclusion, our new cellular model enabled us to reproduce the pathological phenotypes known in the literature, and to demonstrate deregulation of pro-inflammatory cytokine expression in EBS, notably CXCL10 and CXCL11. Taken together, these results make this model a relevant tool to allow a better understanding of the molecular mechanisms associated with the pathology, particularly the inflammatory component, paving the way for new therapeutic approaches
Jin, Yehwa. "Research towards the effective disruption of reproductive competence in Nile tilapia Oreochromis niloticus." Thesis, University of Stirling, 2018. http://hdl.handle.net/1893/28382.
Chai, Shin Luen Chai. "Novel Genetic Modifiers in a Monogenic Cardiac Arrhythmia." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1516618028568975.
Dhanjal, Jaspreet Kaur. "Computational insights into CRISPR/Cas9 system for improved genome editing." Thesis, IIT Delhi, 2019. http://eprint.iitd.ac.in:80//handle/2074/8077.
Rodas, Méndez Ana Lucía. "MtSUPERMAN controls the number of flowers per inflorescence and floral organs in the inner three whorls of Medicago truncatula." Doctoral thesis, Universitat Politècnica de València, 2021. http://hdl.handle.net/10251/171474.
[CA] Les lleguminoses són un gran grup de plantes considerades de gran importància pel seu valor nutricional per a l'alimentació humana i ramadera. A més, les famílies de lleguminoses es caracteritzen per trets distintius de desenrotllament com la seua inflorescència composta i la seua complexa ontogènia floral. Per a comprendre millor estes característiques distintives, és important estudiar els gens reguladors clau involucrats en la inflorescència i el desenrotllament floral. El gen SUPERMAN (SUP) és un factor transcripcional de dits de zinc (Cys2-Hys2) considerat com un repressor actiu que controla el nombre d'estams i carpels en A. thaliana. A més, SUP està involucrat en la terminació del meristemo floral i el desenrotllament dels teixits derivats del carpel. "L'objectiu principal d'este treball va ser la caracterització funcional de l'ortòleg de SUP en la lleguminosa model Medicago truncatula (MtSUP) . Aconseguim l'objectiu amb base en un enfocament genètic invers, anàlisi d'expressió gènica i assajos de complementació i sobreexpressió. Els nostres resultats mostren que MtSUP és el gen ortòleg de SUP en M. truncatula. MtSUP compartix alguns dels rols ja descrits per a SUP amb variacions. Curiosament, MtSUP està involucrat en la determinació del meristemo de la inflorescència secundària (I2) i els primordios comuns (CP). Per tant, MtSUP controla el nombre de flors i pètals-estams que produïxen el meristemo I2 i els primordios comuns, respectivament. MtSUP mostra funcions noves per a un gen tipus SUP, exercint papers clau en els meristemos que conferixen complexitat de desenrotllament a esta família d'angiospermes. "Este treball va permetre identificar a MtSUP, un gen clau que forma part de la xarxa reguladora genètica darrere de la inflorescència composta i el desenrotllament de flors en la lleguminosa model M. truncatula.
[EN] Legumes are a large group of plants considered of great importance for their nutritional value in human and livestock nutrition. Besides, legume families are characterized by distinctive developmental traits as their compound inflorescence and complex floral ontogeny. For a better understanding of these distinctive features is important to study key regulatory genes involved in the inflorescence and floral development. The SUPERMAN (SUP) gene is a zinc-finger (Cys2-Hys2) transcriptional factor considered to be an active repressor that controls the number of stamens and carpels in A. thaliana. Moreover, SUP is involved in the floral meristem termination and the development of the carpel marginal derived tissues. The main objective of this work was the functional characterization of the SUP orthologue in the model legume Medicago truncatula (MtSUP). We achieved this objective based on a reverse genetic approach, gene expression analysis, and complementation and overexpression assays. Our results show that MtSUP is the orthologous gene of SUP in M. truncatula. MtSUP shares some of the roles already described for SUP with variations. Interestingly, MtSUP controls the determinacy of the secondary inflorescence (I2) meristem and the common primordia (CP). Thus, MtSUP controls the number of flowers and petal-stamens produced by the I2 meristem and the common primordia respectively. MtSUP displays novel functions for a SUP-like gene, playing key roles in the meristems that confer developmental complexity to this angiosperm family. This work allowed to identify MtSUP, a key gene that participates in the genetic regulatory network underlying compound inflorescence and flower development in the model legume M. truncatula.
I would like to thanks the Spanish Ministry of Economy and Competitiveness for the grant (MINECO; BIO2016-75485-R) that supported this work. Special thanks to the Generalitat Valenciana for funding my doctorate with the Santiago Grisolía predoctoral scholarships
Rodas Méndez, AL. (2021). MtSUPERMAN controls the number of flowers per inflorescence and floral organs in the inner three whorls of Medicago truncatula [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/171474
TESIS
Valladares, Rodrigo, and Hanna Briheim. "Metoder och tillämpningar av CRISPR-Cas9 i cancerforskning. : Samt hur CRISPR-Cas9 kan implementeras i skolundervisningen." Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-166140.
CRISPR-Cas9 has recently emerged as an effective genome editing tool. The tool derives from an adaptive immune system in prokaryotes. The technology is used for modification of DNA in plants, animals and humans in a simple and inexpensive way. CRISPR-Cas9 has shown great potential in fighting different diseases like cancer which today is a global health issue. It is seen as a promising tool for cancer research when it comes to cancer therapy and drug development. Here we summarize current methods and applications of CRISPR-Cas9 for cancer research. Furthermore, we explore the possibilities of introducing and applying this kind of genetic engineering in biology teaching.
Framläggning, opponering och respondering skedde skriftligt till följd av covid19.