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1

RNA interference ? significance and applications

100%
Stanislawska J., Olszewski W. L.
Archivum Immunologiae et Therapiae Experimentalis
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2005
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vol. 53
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issue 1
39-46
EN
RNA interference (RNAi) is a post-transcriptional, highly conserved process in eukaryotes that leads to specific gene silencing through degradation of the target mRNA. This mechanism is mediated by double-stranded RNA (dsRNA) that is homologous in sequence to the silenced gene. The dsRNA is processed into small interfering RNA (siRNA) by an enzyme called Dicer, and the siRNAs are then incorporated into a multi-component RNA- -induced silencing complex, which finds and cleaves the target mRNA. In plants and worms, amplification of the silencing signal and cell-to-cell RNAi spreading is observed. The proposed biological roles of RNAi include resistance to viruses, transposons (mainly in plants), and the silencing and regulation of gene expression, particularly during development. In developmental gene control, specific small RNAs (micro RNA and small temporal RNA) are involved, which are processed in the same way as dsRNAs but act at the level of translation. RNAi technology has become a powerful tool in functional genomic analyses and may prove to be a useful method to develop highly specific gene-silencing therapeutics against viral infections and cancer in the future.
2

RNA interference-based therapeutics in anticancer therapy

100%
Kaminska B., Kulesza D., Wisniewski P.
Biotechnologia
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2010
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issue 3
94-114
EN
RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing and its discovery led to wide applications. Short interfering RNA (siRNA), which induces RNAi, has been experimentally introduced as a cancer therapy and is expected to be developed as a nucleic acid-based medicine. Potential success of siRNA cancer therapies depends on selection of appropriate gene targets and candidate targets include genes associated with cell proliferation, metastasis, angiogenesis, and drug resistance. In vivo systemic delivery of siRNA-based therapeutics to tumour tissues is challenging and the major limitations of siRNA therapeutic use are its degradation by serum nucleases, poor cellular uptake and rapid renal clearance following systemic administration. Several siRNA-based therapeutics are already in clinical trials. Further development of anti-cancer therapeutic siRNAs depends on development of nanocarriers, nuclease-resistant chemically modified siRNAs and variety of synthetic or natural lipids and polymers to systemically deliver siRNA. Here, we review potential approaches for delivery of RNAi based therapeutic in cancer therapy, results of current studies and clinical trials which demonstrate that the use of targeted siRNA offers promising strategies for cancer therapies.
3

RNA interference:a potential novel therapeutic combating HIV-1 in the central nervous system

100%
Pomerantz R. J.
Archivum Immunologiae et Therapiae Experimentalis
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2004
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vol. 52
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issue 6
401-409
EN
RNA interference (RNAi) is a conserved process by which eukaryotic cells protect their genomes utilizing small, double-stranded RNAs to degrade target RNAs. This occurs in a sequence-specific manner and is different from the interferon effect of larger doublestranded RNAs. Post-transcriptional gene silencing by these nucleic acids can lead to degradation of either cellular or viral RNAs. It has been recently shown that doublestranded, small interfering RNAs (siRNAs) of 21 to 25 nucleotides can be transfected into relevant cells to target specific RNAs. In addition, utilizing hairpin motifs, siRNAs can be expressed intracellularly using molecular therapeutic vectors. This potent approach has been utilized to both inhibit pathogens, including viruses, as well as to dissect cellular molecular mechanisms via a potent knockout effect. At this time in the HIV-1-pandemic, one of the remaining, most enigmatic, and still vitally important areas of HIV-1 pathogenesis occurs in the central nervous system (CNS). HIV-1-induced encephalopathy remains difficult to treat in the developing world and in parts of the developed world, even in the era of highly active anti-retroviral therapy. As such, novel approaches which could lead to intracellular immunization, and life-long resistance against HIV-1 encephalopathy would be of important impact worldwide. Thus, we now seek to combine our background in molecular therapeutics and RNAi with our long-standing interest in HIV-1 neuropathogenesis to target the CNS using siRNAs.
4

Short interfering RNAs as tools for sequence-specific gene silencing

88%
Sierant M., Nawrot B.
Biotechnologia
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2003
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issue 2
84-103
EN
In diverse eukaryotes, dsRNA triggers the destruction of mRNA sharing the same sequence as the dsRNA in the process called RNAi. The guides for sequence-specific degradation of mRNA are 21 nt short interfering RNAs (siRNAs). Synthetic siRNAs can efficiently mediate RNAi, but a drawback of RNAi is its transient nature as a result of the limited availability and stability of synthetic oligonucleotides. Recently, several groups reported the construction of expression plasmid vectors that mediate the production of siRNAs under control of Pol III promoters. These vectors allow the continued expression of siRNAs in the cells resulting in persistent and specific suppression of target genes. The retroviral siRNA expressing system allows for stable inactivation of the genes in primary cells or living organisms.
5

Chemically modified siRNA duplexes

75%
Sierant M.
|
EN
RNA interference (RNAi) is a powerful biological process for a sequence-specific silencing of a gene expression in diverse eukaryotic cells. Discovery of this phenomena had tremendous significance for functional genomics and development of novel gene-specific therapies. The future success of RNAi technology relies on identifying appropriate chemical modifications to improve stability, potency and in vivo cellular delivery of the effector moieties, siRNAs. The presented review attempts to describe some of the biological challenges associated with using synthetic siRNAs to effect RNAi and summarizes the role of the chemical tools in the application of RNAi technology.
6

Perspectives of biotechnology in the management of plant-parasitic nematodes

63%
Dabrowska J., Filipecki M.
Biotechnologia
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2010
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issue 3
173-190
EN
Many laboratories worldwide are involved in the research on effective prevention and management of plant parasitic nematodes. Chemical control of these parasites is very costly and harmful to the environment, though the main strategy is to use resistance genes in breeding programs of crop plants. There is a limited number of naturally occurring resistance genes. Biotechnology can extend the usage of known resistance genes by transferring them to related and unrelated species via plant transformation. However, most promising is the development of new resistance strategies based on RNA interference or specific and inducible overexpression of nematocidal genes. Functional analysis of nematode and plant genes that are involved in induction and development of feeding structures can significantly help in engineering of new sources of resistance. Obviously, biotechnology is not the only prospective solution; however, it significantly enriches the breeders' toolbox. On the other hand, biotechnology-based pest management methods have been developed until recently, and often there are some shortcomings associated which require more research and optimization. Moreover, there is a permanent poor acceptance of genetically modified crops especially in Europe, which influences the decisions of policy makers. Nevertheless, recent genome scale experiments promise significant acceleration in the research and create a portfolio of numerous new possibilities.
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