Aminoacylase I deficiency due to ACY1 mRNA exon skipping

2013 ◽  
Vol 86 (4) ◽  
pp. 367-372 ◽  
Author(s):  
L. Ferri ◽  
S. Funghini ◽  
A. Fioravanti ◽  
E.G. Biondi ◽  
G. la Marca ◽  
...  
Keyword(s):  
Exon Skipping

Muskeldystrophie Typ Duchenne

2011 ◽  
Vol 30 (10) ◽  
pp. 805-812
Author(s):  
A. von Moers
Keyword(s):  
Exon Skipping ◽  
Phase Iii ◽  
Muskeldystrophie Duchenne

ZusammenfassungDie Muskeldystrophie Duchenne ist eine X-gebundene rezessive Erkrankung, die bei 1:3 500 Knaben auftritt. Sie wird durch Mutationen im DMD-Gen verursacht. Die Mutationen resultieren in einem Verlust von Dystrophin, dies führt zur progredienten Muskeldegeneration. Der Krankheitsverlauf ist durch eine progrediente, proximal betonte Muskelschwäche gekennzeichnet, die ohne Behandlung zu einem Gehverlust um das 10. Lebensjahr und zum frühzeitigen Tod um das 20. Lebensjahr durch Ateminsuffizienz oder Herzversagen führt. Durch symptomatische Therapien kann der Krankheitsverlauf positiv beeinflusst werden, besonders durch die Etablierung der nicht invasiven Beatmung konnte die Lebenserwartung erheblich verlängert werden. In den letzten Jahren wurden verschiedene Ansätze einer kausalen Therapie untersucht. Am weitesten gediehen ist das “exon skipping”, dessen Wirksamkeit in internationalen, multizentrischen Phase-III Studien untersucht wird.

Stem Cell-Mediated Exon Skipping of the Dystrophin Gene by the Bystander Effect

2015 ◽  
Vol 15 (6) ◽  
pp. 563-571 ◽  
Author(s):  
Mirella Meregalli ◽  
Andrea Farini ◽  
Clementina Sitzia ◽  
Cyriaque Beley ◽  
Paola Razini ◽  
...  
Keyword(s):  
Stem Cell ◽  
Bystander Effect ◽  
Exon Skipping ◽  
Dystrophin Gene

scholarly journals Alternative splicing landscapes in Arabidopsis thaliana across tissues and stress conditions highlight major functional differences with animals

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Guiomar Martín ◽  
Yamile Márquez ◽  
Federica Mantica ◽  
Paula Duque ◽  
Manuel Irimia
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Alternative Splicing ◽  
Stress Responses ◽  
Target Genes ◽  
Intron Retention ◽  
Single Gene ◽  
Exon Skipping ◽  
Environmental Response ◽  
Biotic Stresses

Abstract Background Alternative splicing (AS) is a widespread regulatory mechanism in multicellular organisms. Numerous transcriptomic and single-gene studies in plants have investigated AS in response to specific conditions, especially environmental stress, unveiling substantial amounts of intron retention that modulate gene expression. However, a comprehensive study contrasting stress-response and tissue-specific AS patterns and directly comparing them with those of animal models is still missing. Results We generate a massive resource for Arabidopsis thaliana, PastDB, comprising AS and gene expression quantifications across tissues, development and environmental conditions, including abiotic and biotic stresses. Harmonized analysis of these datasets reveals that A. thaliana shows high levels of AS, similar to fruitflies, and that, compared to animals, disproportionately uses AS for stress responses. We identify core sets of genes regulated specifically by either AS or transcription upon stresses or among tissues, a regulatory specialization that is tightly mirrored by the genomic features of these genes. Unexpectedly, non-intron retention events, including exon skipping, are overrepresented across regulated AS sets in A. thaliana, being also largely involved in modulating gene expression through NMD and uORF inclusion. Conclusions Non-intron retention events have likely been functionally underrated in plants. AS constitutes a distinct regulatory layer controlling gene expression upon internal and external stimuli whose target genes and master regulators are hardwired at the genomic level to specifically undergo post-transcriptional regulation. Given the higher relevance of AS in the response to different stresses when compared to animals, this molecular hardwiring is likely required for a proper environmental response in A. thaliana.

scholarly journals Evaluating the potential of novel genetic approaches for the treatment of Duchenne muscular dystrophy

2021 ◽  
Author(s):  
Vratko Himič ◽  
Kay E. Davies
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Structural Integrity ◽  
Viral Vector ◽  
Exon Skipping ◽  
Dystrophin Gene ◽  
Pharmacological Treatments ◽  
Genetic Sequencing ◽  
Reading Frame ◽  
Target Effects

AbstractDuchenne muscular dystrophy (DMD) is an X-linked progressive muscle-wasting disorder that is caused by a lack of functional dystrophin, a cytoplasmic protein necessary for the structural integrity of muscle. As variants in the dystrophin gene lead to a disruption of the reading frame, pharmacological treatments have only limited efficacy; there is currently no effective therapy and consequently, a significant unmet clinical need for DMD. Recently, novel genetic approaches have shown real promise in treating DMD, with advancements in the efficacy and tropism of exon skipping and surrogate gene therapy. CRISPR-Cas9 has the potential to be a ‘one-hit’ curative treatment in the coming decade. The current limitations of gene editing, such as off-target effects and immunogenicity, are in fact partly constraints of the delivery method itself, and thus research focus has shifted to improving the viral vector. In order to halt the loss of ambulation, early diagnosis and treatment will be pivotal. In an era where genetic sequencing is increasingly utilised in the clinic, genetic therapies will play a progressively central role in DMD therapy. This review delineates the relative merits of cutting-edge genetic approaches, as well as the challenges that still need to be overcome before they become clinically viable.

scholarly journals Development of antisense-mediated myostatin knockdown for the treatment of insulin resistance

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wouter Eilers ◽  
Mark Cleasby ◽  
Keith Foster
Keyword(s):  
Glucose Uptake ◽  
Muscle Mass ◽  
Exon Skipping ◽  
Negative Regulator ◽  
Intramuscular Administration ◽  
Transcript Levels ◽  
Muscle Disorders ◽  
Intravenous Injections ◽  
Phosphorodiamidate Morpholino Oligomers

AbstractMyostatin is a negative regulator of muscle mass and its inhibition represents a promising strategy for the treatment of muscle disorders and type 2 diabetes. However, there is currently no clinically effective myostatin inhibitor, and therefore novel methods are required. We evaluated the use of antisense phosphorodiamidate morpholino oligomers (PMO) to reduce myostatin expression in skeletal muscle and measured their effects on muscle mass and glucose uptake. C57/Bl6 mice received intramuscular or intravenous injections of anti-myostatin PMOs. Repeated intramuscular administration lead to a reduction in myostatin transcript levels (~ 20–40%), and an increase in muscle mass in chow and high-fat diet (HFD)-fed mice, but insulin-stimulated glucose uptake was reduced in PMO-treated muscles of HFD-fed mice. Five weekly intravenous administrations of 100 nmol PMO did not reduce myostatin expression, and therefore had no significant physiological effects. Unexpectedly, exon skipping levels were higher after intramuscular administration of PMO in HFD- than chow-fed mice. These results suggest that a modest PMO-induced reduction in myostatin transcript levels is sufficient to induce an increase in muscle mass, but that a greater degree of inhibition may be required to improve muscle glucose uptake.

scholarly journals Molecular diversity in amino-terminal domains of human calpastatin by exon skipping.

1992 ◽  
Vol 267 (12) ◽  
pp. 8437-8442
Author(s):  
W.J. Lee ◽  
H Ma ◽  
E Takano ◽  
H.Q. Yang ◽  
M Hatanaka ◽  
...  
Keyword(s):  
Molecular Diversity ◽  
Exon Skipping ◽  
Amino Terminal ◽  
Terminal Domains
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