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 22 for “"Exon Skipping"”.
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Machine learning based CRISPR gRNA design for therapeutic exon skipping
The restoration of gene function by the induced skipping of a deleterious exon has been shown to be effective for treating genetic disorders. However, many of the clinically successful therapies for exon skipping are transient oligonucleotide-based treatments that require frequent dosing. …
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Exon skipping therapy for Duchenne Muscular Dystrophy with CRISPR base editors
Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01
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Genexpression des Adaptorproteins Shc bei Patienten mit Juveniler Myelomonozytärer Leukämie (JMML)
… und K562 erhöhte Werte. Es wurde alternatives 'Exon Skipping' von Exon 12 beobachtet. Exon 12 kodiert für die SH2-Domäne von Shc. Drei Formen alternativen Spleißens wurden beschrieben. Zuvor wurde die genomische DNA dieses Bereiches sequenziert. Fünf Introns von 83 bp bis 1607 bp Länge wurden …
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Identification, improved modeling and integration of signals to predict constitutive and altering splicing
… algorithm, ACEScan, which distinguishes exons subject to evolutionarily conserved alternative splicing from constitutively spliced or lineage-specifically-spliced exons is described; (v) The genome-wide search for and experimental validation of exon-skipping events using the combination …
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Characterization and Development of Strategies for Altering Protein Expression in JSL1 Cells
… differentially including or excluding variable exons provides a means for increasing proteome complexity. Alternative gene splicing occurs in a cell specific manner and may be influenced by changes in the extracellular environment. Despite the importance of this method for regulating gene …
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RNA-based therapeutic approaches for FTDP-17
… tools for FTDP-17. CHAPTER 2 explores an exon skipping strategy to modulate splice defects in the context of FTD-17 using small nuclear RNAs (snRNAs). CHAPTER 3 is based on a short interfering RNA (siRNA) approach to modulate post-transcriptional gene silencing of specific isoform …
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BIOINFORMATICS ANALYSIS OF FULL-LENGTH RNA NANOPORE SEQUENCING AT SINGLE CELL LEVEL TO STUDY TRANSCRIPTIONAL AND MUTATIONAL PATTERNS IN HUMAN LEUKEMIA
… splicing pattern analyses revealed prevalent exon skipping and intron retention in AML samples. AML cells with the SRSF2 mutation exhibited significantly higher proportions of genes with multiple isoforms or novel transcripts. These findings illuminate the intricate connections between genetic …
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Genetic correction of Parkinson’s disease using CRISPR-SKIP
… cells to produce less toxic isoforms of SNCA by skipping the exons that encode for the domains responsible for aggregation. Thus, one potential approach to treat PD is skipping exon 3 in SNCA, which has been shown to decrease α-synuclein aggregation. We have recently demonstrated that CRISPR-Cas9 …
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Alternative expression forms of the bovine αₛ₁-casein gene
… it has a 13 amino acid (encoded by the entire exon 4 of the αₛ₁-casein gene) deletion, which significantly alters the physico-chemical properties of the protein. Previous work suggested that the deletion is caused by exon 4 skipping during RNA processing and that a T→A transversion mutation at …
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Prevention of Duchenne Muscular Dystrophy by CRISPR/Cas Therapeutic Genome Editing
… gene on the X chromosome, which consists of 79 exons encoding dystrophin protein. Patients with DMD develop progressive muscle weakness and cardiomyopathy, and ultimately succumb to respiratory and cardiac failure in their mid-20s. The dystrophin gene was identified three decades ago and …
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Precision Gene Editing for Muscle Diseases
… associated with DMD and HCM. For DMD, I employ exon skipping, a technique that modifies the processing of mature mRNA to produce an internally truncated but functional dystrophin protein. This proof-of-concept approach holds great promise for the treatment of this X-linked recessive disease. For …
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Mechanisms of Genome Buffering and Cell Fate Coordination in Adult Tissue Homeostasis
… entry sites (IRES), b) the induction of exon skipping due to compromised exon splicing enhancers (ESEs), and c) the conversion of pseudo-mRNAs to protein-coding mRNAs due to the unwanted elimination of premature termination codons. I propose that these molecular events serve as …
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Regulation of Human Telomerase Alternative Splicing
… region of 38 bp repeats (block 6) ~2 kb from the exon/intron junctions is essential for the exclusion of exons 7 and 8. Block 6 repeats suggested that RNA:RNA pairing may regulate splicing of hTERT. Mutations within the repeat sequence that abolish exon skipping were corrected by compensatory …
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Ανάλυση των μοτίβων ματίσματος σε γονίδια που εμπλέκονται στην πρώιμη εκδήλωση Συστηματικού Ερυθηματώδους Λύκου
… σε τέσσερις κατηγορίες: παράλειψη εξονίων (exon skipping), συγκράτηση ιντρονίων (intron retention) και εναλλακτικά σημεία δότη-λήπτη (alternative donor and acceptor sites). Βιβλιογραφικά δεδομένα υποδηλώνουν ότι η συγκράτηση ιντρονίων μπορεί να λειτουργεί ως ρυθμιστικός μηχανισμός που οδηγεί …
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Development of Novel Therapies for Marfan Syndrome using a Human iPSC-disease model
… the level of the pathological mutation using an exon skipping approach and (ii) designing an unbiased phenotypic drug screen to identify putative compounds able to rescue abnormal proteolysis in our disease model. These complementary techniques will enable the identification of novel …
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Isoform-Specific Expression During Embryo Development in Arabidopsis and Soybean
… targets. We identified several instances of exon skipping and intron retention as products of alternative splicing. The coding potential of the splice variants were evaluated using CodeWise. I developed CodeWise, a weighted support vector machine classifier to assess the coding potential of …
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The splice variants of TREK-1 act as dominant-negative suppressors of human uterine relaxation: Implications for preterm labor
… as SV-1 to SV-5 due to the number of deleted exons. The exon skipping contributes to heavily truncated proteins with defective TREK-1 channel properties. Quantitative real-time PCR provided evidence of elevated expression of SV-5 in preterm labor, while TREK-1 was down-regulated. The …
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Mechanistic Investigation of Genotype-Phenotype Correlations in PIK3R1-Related Diseases
… final part of this thesis focussed on a PIK3R1 exon skipping mutant (p85$\alpha$ $\Delta$Ex11) that confers PI3K activation in lymphocytes and causes APDS2. APDS2 patients have an immune-restricted phenotype, even though the mutation occurs within the ubiquitously expressed PIK3R1. To …
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Identifying Splicing Regulatory Elements with de Bruijn Graphs
… experimental evidence to identify SREs found in exons. In my approach, SREs are not restricted to a fixed length (i.e., k-mers, for a fixed k). Consequently, the predicted SREs are of different lengths. I identified 2001 putative exonic enhancers and 3080 putative exonic silencers for human …
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Computational analyses of non-canonical architectural and structural features associated with alternative splicing
… features that are related to atypical exon-intron structures and DNA/RNA conformations. First, I studied a group of extremely small exons, known as microexons (≤30 nucleotides), which were shown to be part of an evolutionarily conserved network of neuronal alternative splicing events …
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