scholarly journals Low immunogenicity of LNP allows repeated administrations of CRISPR-Cas9 mRNA into skeletal muscle in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eriya Kenjo ◽  
Hiroyuki Hozumi ◽  
Yukimasa Makita ◽  
Kumiko A. Iwabuchi ◽  
Naoko Fujimoto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exon Skipping ◽  
Repeated Administration ◽  
Great Promise ◽  
Muscle Disorders ◽  
Exon Sequence ◽  
Muscle Groups ◽  
Skeletal Muscle Disorders ◽  
Cas9 Mrna

AbstractGenome editing therapy for Duchenne muscular dystrophy (DMD) holds great promise, however, one major obstacle is delivery of the CRISPR-Cas9/sgRNA system to skeletal muscle tissues. In general, AAV vectors are used for in vivo delivery, but AAV injections cannot be repeated because of neutralization antibodies. Here we report a chemically defined lipid nanoparticle (LNP) system which is able to deliver Cas9 mRNA and sgRNA into skeletal muscle by repeated intramuscular injections. Although the expressions of Cas9 protein and sgRNA were transient, our LNP system could induce stable genomic exon skipping and restore dystrophin protein in a DMD mouse model that harbors a humanized exon sequence. Furthermore, administration of our LNP via limb perfusion method enables to target multiple muscle groups. The repeated administration and low immunogenicity of our LNP system are promising features for a delivery vehicle of CRISPR-Cas9 to treat skeletal muscle disorders.

Activities of creatine kinase and its isoenzymes in serum in various skeletal muscle disorders.

1988 ◽  
Vol 34 (12) ◽  
pp. 2460-2462 ◽  
Author(s):  
J Arenas ◽  
V Diaz ◽  
G Liras ◽  
E Gutierrez ◽  
I Santos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Clinical Features ◽  
Principal Factor ◽  
Isoenzyme Pattern ◽  
Type I ◽  
Isoenzyme Analysis ◽  
Muscle Disorders ◽  
Total Creatine ◽  
Skeletal Muscle Disorders

Abstract We studied possible correlations between anatomopathological and clinical features and the values for total creatine kinase (CK; EC 2.7.3.2) and its isoenzymes, including the proportion of CK-MB, in a population displaying several neuromuscular pathologies. Although we observed no specific isoenzyme pattern associated with the different myopathies, we found isoenzyme analysis useful in studying the histopathological evolution of illness. We also considered whether the pathology was regenerative or nonregenerative, and what type of fiber (I or II) was involved. High CK-MB percentages (greater than 6%) were associated with regenerative and type I fiber myopathies, with regenerative type tissues being the principal factor associated with an increasing proportion of CK-MB. Studying the changes in CK-MB percentage in serum appears to be useful in discriminating neuromuscular from myocardial pathologies.

scholarly journals Is Gene-Size an Issue for the Diagnosis of Skeletal Muscle Disorders?

2020 ◽  
Vol 7 (3) ◽  
pp. 203-216 ◽  
Author(s):  
Marco Savarese ◽  
Salla Välipakka ◽  
Mridul Johari ◽  
Peter Hackman ◽  
Bjarne Udd
Keyword(s):  
Skeletal Muscle ◽  
Muscle Disorders ◽  
Gene Size ◽  
Skeletal Muscle Disorders

Gene Therapy of Skeletal Muscle Disorders Using Viral Vectors

Muscle ◽  
2012 ◽  
pp. 1045-1051 ◽  
Author(s):  
Andrea L.H. Arnett ◽  
Julian N. Ramos ◽  
Jeffrey S. Chamberlain
Keyword(s):  
Skeletal Muscle ◽  
Gene Therapy ◽  
Viral Vectors ◽  
Muscle Disorders ◽  
Skeletal Muscle Disorders

scholarly journals Impact of Melatonin on Skeletal Muscle and Exercise

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 288 ◽  
Author(s):  
Alessandra Stacchiotti ◽  
Gaia Favero ◽  
Luigi Fabrizio Rodella
Keyword(s):  
Quality Of Life ◽  
Skeletal Muscle ◽  
Human Aging ◽  
Muscle Disorders ◽  
Age Related ◽  
Anti Oxidant ◽  
Therapeutic Tools ◽  
Skeletal Muscle Disorders ◽  
Preclinical And Clinical Studies

Skeletal muscle disorders are dramatically increasing with human aging with enormous sanitary costs and impact on the quality of life. Preventive and therapeutic tools to limit onset and progression of muscle frailty include nutrition and physical training. Melatonin, the indole produced at nighttime in pineal and extra-pineal sites in mammalians, has recognized anti-aging, anti-inflammatory, and anti-oxidant properties. Mitochondria are the favorite target of melatonin, which maintains them efficiently, scavenging free radicals and reducing oxidative damage. Here, we discuss the most recent evidence of dietary melatonin efficacy in age-related skeletal muscle disorders in cellular, preclinical, and clinical studies. Furthermore, we analyze the emerging impact of melatonin on physical activity. Finally, we consider the newest evidence of the gut–muscle axis and the influence of exercise and probably melatonin on the microbiota. In our opinion, this review reinforces the relevance of melatonin as a safe nutraceutical that limits skeletal muscle frailty and prolongs physical performance.

Transforming growth factor-?2 is elevated in skeletal muscle disorders

1999 ◽  
Vol 22 (7) ◽  
pp. 889-898 ◽  
Author(s):  
Nobuyuki Murakami ◽  
Ian S. McLennan ◽  
Ikuya Nonaka ◽  
Kyoko Koishi ◽  
Christina Baker ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Muscle Disorders ◽  
Skeletal Muscle Disorders

scholarly journals Proteomic profiling of animal models mimicking skeletal muscle disorders

2007 ◽  
Vol 1 (9) ◽  
pp. 1169-1184 ◽  
Author(s):  
Philip Doran ◽  
Joan Gannon ◽  
Kathleen O'Connell ◽  
Kay Ohlendieck
Keyword(s):  
Skeletal Muscle ◽  
Animal Models ◽  
Proteomic Profiling ◽  
Muscle Disorders ◽  
Skeletal Muscle Disorders

scholarly journals FMO1 catalyzes the production of taurine from hypotaurine

2019 ◽  
Author(s):  
Sunil Veeravalli ◽  
Ian R. Phillips ◽  
Rafael T. Freire ◽  
Dorsa Varshavi ◽  
Jeremy R. Everett ◽  
...  
Keyword(s):  
De Novo ◽  
Cysteic Acid ◽  
Muscle Disorders ◽  
H Nmr ◽  
Drug Metabolizing Enzyme ◽  
Anti Oxidant ◽  
Metabolizing Enzyme ◽  
Skeletal Muscle Disorders

ABSTRACTTaurine is one of the most abundant amino acids in mammalian tissues. It is obtained from the diet and by de novo synthesis, from cysteic acid or hypotaurine. Despite the discovery in 1954 that the oxygenation of hypotaurine produces taurine, the identification of an enzyme catalyzing this reaction has remained elusive. In large part this is due to the incorrect assignment, in 1962, of the enzyme as a NAD-dependent hypotaurine dehydrogenase. For more than 55 years the literature has continued to refer to this enzyme as such. Here we show, both in vivo and in vitro, that the enzyme that oxygenates hypotaurine to produce taurine is flavin-containing monooxygenase 1 (FMO1). Metabolite analysis of the urine of Fmo1-null mice by 1H NMR spectroscopy revealed a build-up of hypotaurine and a deficit of taurine in comparison with the concentrations of these compounds in the urine of wild-type mice. In vitro assays confirmed that FMO1 of human catalyzes the conversion of hypotaurine to taurine utilizing either NADPH or NADH as co-factor. FMO1 has a wide substrate range and is best known as a xenobiotic- or drug-metabolizing enzyme. The identification that the endogenous molecule hypotaurine is a substrate for the FMO1-catalyzed production of taurine resolves a long-standing mystery. This finding should help establish the role FMO1 plays in a range of biological processes in which taurine or its deficiency is implicated, including conjugation of bile acids, neurotransmitter, anti-oxidant and anti-inflammatory functions, the pathogenesis of obesity and skeletal muscle disorders.

scholarly journals Muscling in on the third dimension

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Mohsen Afshar Bakooshli ◽  
Penney M Gilbert
Keyword(s):  
Skeletal Muscle ◽  
Muscle Tissue ◽  
Human Skeletal Muscle ◽  
Three Dimensional ◽  
Dimensional Model ◽  
Three Dimensional Model ◽  
Muscle Disorders ◽  
The Third ◽  
Third Dimension ◽  
Skeletal Muscle Disorders

The development of a functional three-dimensional model of human skeletal muscle tissue could accelerate progress towards new and personalized treatments for skeletal muscle disorders.

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