Effect of Intramuscular and Intraperitoneal Injections of conjugated MSTN-siRNA-cholesterol on Inhibition of Myostatin Gene expression
محل انتشار: مجله سلول و تحقیقات مولکولی، دوره: 14، شماره: 1
سال انتشار: 1401
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 104
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شناسه ملی سند علمی:
JR_JCMR-14-1_003
تاریخ نمایه سازی: 17 آبان 1401
چکیده مقاله:
Myostatin (MSTN) is primarily expressed in skeletal muscle tissue and acts as a negative regulator of skeletal muscle growth by inhibiting differentiation and proliferation of myoblasts. Inhibition of MSTN expression could result in muscular hypertrophy. An effective therapeutic approach based on specific silencing of a target gene is provided by RNA interference. The distribution of biologically active small interfering RNAs (siRNAs) inside the target cells/ tissue, is a significant problem due to the limited stability and delivery of siRNAs. Strategies depending on vector delivery have also a limited clinical utility due to safety concerns. Thus direct application of active siRNAs in vivo is the preferred strategy. We described the efficiency of intramuscular and intraperitoneal injections of MSTN-siRNA conjugated with cholesterol into the skeletal muscle of mice. The designed siRNA molecule was complementary to the exon II of the mouse MSTN gene. Mice were injected with a weekly dose of ۱۰ μg/kg conjucated siRNA-cholesterol intraperitoneally or intramuscularly. Our findings suggested that within a few weeks of application, siRNA-treated mice showed a significant increase in muscle mass and suppressed MSTN gene expression. Even though both types of injections increased muscle weight, intramuscular siRNA injections suppressed the MSTN gene more effectively, whereas intraperitoneal RNA injections had a more significant impact on total body weight. The cholesterol-conjugated siRNA platform discussed here may hold promise for treating several skeletal muscle-related diseases, such as atrophic muscle disease, muscular dystrophy, and type II diabetes.
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نویسندگان
Mitra Riasi
Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran
Sina Mozaffari Jovin
Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Ali Javadmanesh
Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran
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