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Antisense Molecules (antisense + molecule)
Selected AbstractsInnovations in oligonucleotide drug deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2003Melanie A. Lysik Abstract Oligonucleotides (ONs) are a new class of therapeutic compounds under investigation for the treatment of a variety of disease states, such as cancer and HIV, and for FDA approval of an anti-CMV retinitis antisense molecule (VitraveneÔ, Isis Pharmaceuticals). However, these molecules are limited not only by poor cellular uptake, but also by a general lack of understanding regarding the mechanism(s) of ON cellular uptake. As a result, various delivery vehicles have been developed that circumvent the proposed mechanism of uptake, endocytosis, while improving target specific delivery and/or drug stability. This review describes various traditional and novel delivery mechanisms that have been employed to improve ON cellular delivery, cost effectiveness, and therapeutic efficacy. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1559,1573, 2003 [source] Gene Knockdown: A Powerful Tool for Gene Function Study in FishJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 3 2008Surintorn Boonanuntanasarn So far, there are a number of fish genome projects, including experimental and economically important fish that provide available DNA sequence information. However, the function of a gene cannot be deduced only by its DNA sequence. Therefore, a technique with which to investigate the function of the fish gene is needed. Gene knockdown (GKD), or antisense technology, is now being used as a powerful technique to study gene functions in living organisms. GKD effects result from the introduction of an antisense molecule into living cells. The antisense agents bind to target messenger RNA, thus inactivating the target gene expression. The appropriately spatial inhibitory effects on protein production from corresponding gene resulted in the phenotypic change. Therefore, the function of the gene can be understood. To date, there are a number of antisense molecules that can affect efficient GKD in fish. These include antisense oligonucleotides, small interfering RNA, and ribozyme. These antisense molecules cause specific gene inhibitor effects with different mechanisms. The various antisense mechanism types facilitate a number of GKD applications with various approaches in animals. In this review, we demonstrate the characteristics of each antisense molecule, its mechanism, and its application, especially for gene functional analysis in fish. [source] Retinal patterning by Pax6-dependent cell adhesion moleculesDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2010Elisabeth Rungger-Brändle Abstract Long-standing evidence gained from Pax6 mutant embryos pointed to an involvement of Pax6-dependent cell adhesion molecules in patterning the central nervous system and, in particular, the retina. However, direct evidence for such pathways remained elusive. We here present direct evidence that knockdown of Pax6 expression by morpholino antisense molecules in Xenopus embryos and knockdown of maternal N-cadherin (mNcad), N-cadherin (Ncad) and neural cell adhesion molecule (NCAM) produce similar phenotypes. Eye formation is reduced and retinal lamination is heavily disorganized. In Pax6 knockdown embryos, the levels of mRNAs coding for these cell adhesion molecules are markedly reduced. Overexpression of Pax6 efficiently rescues the phenotype of Pax6 knockdown embryos and restores expression of these putative target genes. Rescue of Pax6-deficiency by the putative target gene mNcad moderately rescues eye formation. The promoters of the genes coding for cell adhesion molecules contain several putative Pax6 binding sites, as determined by computer analysis. Chromatin immunoprecipitation shows that, in embryonic heads, Pax6 binds to promoter regions containing such predicted binding sites. Thus, several cell adhesion molecules are direct target genes of Pax6 and cooperate in retinal patterning. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 764,780, 2010 [source] RNA interference in pain researchJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Thomas Röhl Abstract Within the course of only the last few years, RNA interference (RNAi) has been established as a standard technology for investigation of protein function and target validation. The present review summarizes recent progress made in the application of RNAi in neurosciences with special emphasis on pain research. RNAi is a straightforward method to generate loss-of-function phenotypes for any gene of interest. In mammals, silencing is induced by small interfering RNAs (siRNAs), which have been shown to surpass traditional antisense molecules. Due to its high specificity, RNAi has the potential for subtype selective silencing of even closely related genes. One of the major challenges for in vivo investigations of RNAi remains efficient delivery of siRNA molecules to the relevant tissues and cells, particularly to the central nervous system. Various examples will be given to demonstrate that intrathecal application of siRNAs is a suitable approach to analyse the function of receptors or other proteins that are hypothesized to play an important role in pain signalling. Intensive efforts are currently ongoing to solve remaining problems such as the risk of off-target effects, the stability of siRNA molecules and their efficient delivery to the CNS. RNAi has thus demonstrated that it is an extremely valuable tool for the development of new analgesic drugs. [source] Gene Knockdown: A Powerful Tool for Gene Function Study in FishJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 3 2008Surintorn Boonanuntanasarn So far, there are a number of fish genome projects, including experimental and economically important fish that provide available DNA sequence information. However, the function of a gene cannot be deduced only by its DNA sequence. Therefore, a technique with which to investigate the function of the fish gene is needed. Gene knockdown (GKD), or antisense technology, is now being used as a powerful technique to study gene functions in living organisms. GKD effects result from the introduction of an antisense molecule into living cells. The antisense agents bind to target messenger RNA, thus inactivating the target gene expression. The appropriately spatial inhibitory effects on protein production from corresponding gene resulted in the phenotypic change. Therefore, the function of the gene can be understood. To date, there are a number of antisense molecules that can affect efficient GKD in fish. These include antisense oligonucleotides, small interfering RNA, and ribozyme. These antisense molecules cause specific gene inhibitor effects with different mechanisms. The various antisense mechanism types facilitate a number of GKD applications with various approaches in animals. In this review, we demonstrate the characteristics of each antisense molecule, its mechanism, and its application, especially for gene functional analysis in fish. [source] | ||||||||||