• MeSH
• biotechnologie MeSH
• klinické laboratorní techniky MeSH
• malá interferující RNA MeSH
• molekulární biologie MeSH
• RNA interference fyziologie   MeSH
• RNA MeSH

• Konspekt
• Biotechnologie. Genetické inženýrství
• NLK Obory
• biomedicínské inženýrství

• MeSH
• geny MeSH
• RNA MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• genetika, lékařská genetika

RNA interference (RNAi) denotes sequence-specific mRNA degradation induced by long double-stranded RNA (dsRNA). RNAi is an ancient eukaryotic defense mechanism against viruses and mobile elements. In mammals, endogenous RNAi was outstripped during evolution by the current innate and acquired immunity. The RNAi apparatus, which remains essentially intact, serves mostly the microRNA pathway, which regulates endogenous gene expression. Remarkably, several recent publications brought the mammalian endogenous RNAi pathway back into the spotlight. Here, I will provide an up-to-date review of the mammalian endogenous RNAi pathway with a focus on its defensive role and overlaps with miRNA and piRNA pathways.

• MeSH
• lidé MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• RNA interference * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Nonalcoholic steatohepatitis (NASH) is a severe liver disorder characterized by triglyceride accumulation, severe inflammation, and fibrosis. With the recent increase in prevalence, NASH is now the leading cause of liver transplant, with no approved therapeutics available. Although the exact molecular mechanism of NASH progression is not well understood, a widely held hypothesis is that fat accumulation is the primary driver of the disease. Therefore, diacylglycerol O-acyltransferase 2 (DGAT2), a key enzyme in triglyceride synthesis, has been explored as a NASH target. RNAi-based therapeutics is revolutionizing the treatment of liver diseases, with recent chemical advances supporting long-term gene silencing with single subcutaneous administration. Here, we identified a hyper-functional, fully chemically stabilized GalNAc-conjugated small interfering RNA (siRNA) targeting DGAT2 (Dgat2-1473) that, upon injection, elicits up to 3 months of DGAT2 silencing (>80%-90%, p < 0.0001) in wild-type and NSG-PiZ "humanized" mice. Using an obesity-driven mouse model of NASH (ob/ob-GAN), Dgat2-1473 administration prevents and reverses triglyceride accumulation (>85%, p < 0.0001) without increased accumulation of diglycerides, resulting in significant improvement of the fatty liver phenotype. However, surprisingly, the reduction in liver fat did not translate into a similar impact on inflammation and fibrosis. Thus, while Dgat2-1473 is a practical, long-lasting silencing agent for potential therapeutic attenuation of liver steatosis, combinatorial targeting of a second pathway may be necessary for therapeutic efficacy against NASH.

• MeSH
• diacylglycerol-O-acyltransferasa genetika   metabolismus   MeSH
• fibróza MeSH
• játra metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši obézní MeSH
• myši MeSH
• nealkoholová steatóza jater * farmakoterapie   terapie   MeSH
• obezita genetika   terapie   MeSH
• terapie založená na RNAi MeSH
• triglyceridy metabolismus   terapeutické užití   MeSH
• zánět metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• Nobelova cena MeSH
• RNA interference MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biologie
• humanitní vědy a umění

RNA interference (RNAi), a sequence-specific mRNA degradation induced by double-stranded RNA (dsRNA), is a common approach employed to specifically silence genes. Experimental RNAi in plant and invertebrate models is frequently induced by long dsRNA. However, in mammals, short RNA molecules are used preferentially since long dsRNA can provoke sequence-independent type I interferon response. A notable exception are mammalian oocytes where the interferon response is suppressed and long dsRNA is a potent and specific trigger of RNAi. Transgenic RNAi is an adaptation of RNAi allowing for inducing sequence-specific silencing upon expression of dsRNA. A decade ago, we have developed a vector for oocyte-specific expression of dsRNA, which has been used to study gene function in mouse oocytes on numerous occasions. This review provides an overview and discusses benefits and drawbacks encountered by us and our colleagues while working with the oocytes-specific transgenic RNAi system.

• MeSH
• myši transgenní MeSH
• myši MeSH
• oocyty metabolismus   MeSH
• RNA interference * MeSH
• vývojová regulace genové exprese fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The discovery of RNA interference (RNAi) in 1998 ushered in a new era in biology. RNAi currently serves as a favorite approach for inhibition of gene function in many areas of research. This article provides a brief review of RNAi and discussion of the benefits and drawbacks of using long double-stranded RNA (dsRNA) in mammalian oocytes and early embryos. We also provide an introduction to protocols for RNAi experiments in mouse, including preparation and microinjection of dsRNA into mouse oocytes and early embryos, and preparation and testing of constructs for transgenic RNAi based on long hairpin RNA expression.

• MeSH
• embryo savčí cytologie   MeSH
• genetické techniky MeSH
• myši transgenní MeSH
• myši MeSH
• oocyty cytologie   metabolismus   MeSH
• RNA interference MeSH
• transgeny MeSH
• umlčování genů MeSH
• vývojová biologie metody   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The RNA interference (RNAi) and interferons have been an uneasy marriage. Ever since the discovery of RNAi in mammals, the interferon response has been a feared problem. While RNAi became an efficient and widespread method for gene silencing in mammals, numerous studies recognized several obstacles, including undesirable activation of the interferon response, which need to be overcome to achieve a specific and robust RNAi effect. The aim of this text is to provide theoretical and practical information for scientists who want to control interferon response and other adverse effects in their RNAi experiments.

• MeSH
• DNA primery MeSH
• dvouvláknová RNA MeSH
• HEK293 buňky MeSH
• HeLa buňky MeSH
• interferony metabolismus   MeSH
• klonování DNA MeSH
• lidé MeSH
• malá interferující RNA genetika   MeSH
• molekulární sekvence - údaje MeSH
• regulace genové exprese MeSH
• RNA interference MeSH
• sekvence aminokyselin MeSH
• umlčování genů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• Caenorhabditis elegans genetika   MeSH
• Drosophila melanogaster genetika   MeSH
• hmyzí geny MeSH
• malá interferující RNA genetika   MeSH
• messenger RNA MeSH
• RNA interference MeSH
• savci genetika   MeSH

• MeSH
• genetická terapie metody   trendy   MeSH
• komplex RISC terapeutické užití   MeSH
• malá interferující RNA MeSH
• RNA interference MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biologie
• biochemie