China
Africa
Explore chapters and articles related to this topic
Epigenetic control of cell fate and behavior
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
Recently, small RNAs have been described to play large roles in mediating states of cellular differentiation through modulating gene expression states, generally through silencing mechanisms. Small double-stranded RNA molecules, called pre-microRNAs (pre-miRNA), are produced from target genes and processed by the RNA-induced silencing complex (RISC) containing the Dicer protein (Krol et al. 2004). Dicer cleaves the double-stranded structure into two single strands, one of which is the complement of the target gene transcript. The single-stranded mature miRNA then associates with a member of the Argonaute family of proteins, which facilitates base pairing between the miRNA and the target messenger RNA (mRNA). The formation of the new double-stranded structure results in the degradation of the target mRNA, which can no longer be translated to produce a functional protein (Valencia-Sanzhez et al. 2006). The complement of miRNAs within a cell differs based on cell identity and appears to be important in directing the proper development of tissues within an organism (Sayed and Abdellatif 2011). Taken together, the myriad of epigenetic control mechanisms can largely influence states of cellular differentiation, a process that we must hope to control within the context of directed regeneration of complex structures.
Lipid-Based Nanoparticles for siRNA Delivery
Published in Yubing Xie, The Nanobiotechnology Handbook, 2012
Bo Yu, L. James Lee, Robert J. Lee
RNA interference (RNAi) is a potent and specific gene silencing mechanism. Endogenous small RNAs, called microRNAs (miRNA), which function at the translational level, have been shown to regulate important genes associated with cell development, differentiation, and death (Aagaard and Rossi 2007, Kim and Rossi 2007, Pecot et al. 2011). In contrast, siRNAs are typically custom designed, synthetic molecules that mediate gene silencing at the transcription level. siRNA is double-stranded RNA chain 19–23 nt in length (Fire et al. 1998, Aagaard and Rossi 2007). In siRNA-mediated RNAi, siRNA first interacts with Argonaute-2 (Ago-2) to form RNA-induced silencing complexes (RISCs). The sense strand of the siRNAs is then cleaved and the antisense strand seeks out and selectively degrades mRNAs with the complementary sequence, thus preventing translation of the target mRNA into protein, i.e., “silencing” the gene (Whitehead et al. 2009). This RISC-based mechanism is highly efficient. In theory, siRNAs can be designed to inhibit any gene target, including those that are difficult to modulate selectively with traditional small molecules or with antibodies. In addition, a relatively low dosage is required for siRNA-mediated gene silencing due to its high potency. For these reasons, siRNA-based RNAi has been widely utilized for gene-function analysis and drug-target validation in drug development (Kim and Rossi 2007, Pecot et al. 2011).
Computational Sequence- and NGS-Based MicroRNA Prediction
Published in Ervin Sejdić, Tiago H. Falk, Signal Processing and Machine Learning for Biomedical Big Data, 2018
Mature miRNA strands are bound to Argonaute proteins in an RNA-induced silencing complex (RISC), which guide the miRNA to target mRNA regions. The binding of miRNA to mRNA inhibits ribosomal activity, preventing the expression of the protein that is regulated by the miRNA [23].
Preparation and characterization of novel albumin-sericin nanoparticles as siRNA delivery vehicle for laryngeal cancer treatment
Published in Preparative Biochemistry and Biotechnology, 2019
Eda Yalcin, Goknur Kara, Ekin Celik, Ferda Alpaslan Pinarli, Guleser Saylam, Ceren Sucularli, Serhat Ozturk, Esin Yilmaz, Omer Bayir, Mehmet Hakan Korkmaz, Emir Baki Denkbas
RNA interference (RNAi) has become a widely used powerful tool in gene functional analyses and therapeutic applications since it has first emerged as a post-transcriptional gene silencing strategy in 1998.[1,2] This process provides sequence-specific degradation of the target mRNA and hence inhibits translation of the target protein via the key role of siRNA. In this mechanism, the double-stranded RNAs (dsRNAs) are cleaved by the enzyme called Dicer and divided into fragments of 21–23 nucleotides which are called siRNAs. These siRNAs, consisting of a passenger strand and a guide strand, bind to the RNA-Induced Silencing Complex (RISC). Subsequently, the guide strand is complementarily directed to the target mRNA by the activity of Argonaute-2 enzyme to cleave between the 10th and 11th bases of the mRNA.[3] siRNAs can be also produced synthetically with unique sequences that are highly specific to the target. siRNAs have been studied commonly for cancer treatment owing to their high potency for gene silencing.[4] Despite this great potential, a number of drawbacks must be considered for its therapeutic use. The difficulty in delivery of the siRNA molecule to the targeted area resulting from its rapid enzymatic degradation and insufficient cellular uptake is the major obstacle.[4] Therefore, an efficient carrier is still a need in siRNA therapies, and lately, nanoparticles have come forward as favorable delivery systems for safe siRNA transportation and accomplishment of effective gene knockdown in targeted cells.