Patent
Rna interference mediating small rna molecules
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TLDR
In this article, the authors demonstrate that 19-23 nt short RNA fragments are the sequence-specific mediators of RNA interference in a Drosophila in vitro system, and provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNA complex.Abstract:
Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 19-23 nt short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3′ ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.read more
Citations
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Modulation of hiv replication by rna interference
Mario Stevenson,Jean Marc Jacque +1 more
TL;DR: In this article, small interfering RNAs (siRNAs) and vectors encoding one or more siRNAs (including short hairpin siRNA) that are sufficiently homologous to a portion of the HIV genome to mediate RNA interference in vivo are discussed.
Patent
Rna sequence-specific mediators of rna interference
TL;DR: In this paper, a Drosophila in vitro system was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length.
PatentDOI
Sequence-specific inhibition of small RNA function
TL;DR: The RISC inactivators of the present invention enable a variety of methods for identifying and characterizing miRNAs and siRNAs, RISC-associated factors, and agents capable of modulating RNA silencing.
Patent
Methods and compositions for rna interference
TL;DR: In this paper, a hairpin RNA was used to attenuate gene expression in a cell, especially in a mammalian cell, using gene-targeted double stranded RNA (dsRNA).
References
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Journal ArticleDOI
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Andrew Fire,SiQun Xu,Mary K. Montgomery,Steven A. Kostas,Steven A. Kostas,Samuel E. Driver,Craig C. Mello +6 more
TL;DR: To their surprise, it was found that double-stranded RNA was substantially more effective at producing interference than was either strand individually, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
Journal ArticleDOI
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
Journal ArticleDOI
The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
TL;DR: Two small lin-4 transcripts of approximately 22 and 61 nt were identified in C. elegans and found to contain sequences complementary to a repeated sequence element in the 3' untranslated region (UTR) of lin-14 mRNA, suggesting that lin- 4 regulates lin- 14 translation via an antisense RNA-RNA interaction.
Journal ArticleDOI
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
TL;DR: 21-nucleotide siRNA duplexes provide a new tool for studying gene function in mammalian cells and may eventually be used as gene-specific therapeutics.
Journal ArticleDOI
Role for a bidentate ribonuclease in the initiation step of RNA interference
TL;DR: Dicer is a member of the RNase III family of nucleases that specifically cleave double-stranded RNAs, and is evolutionarily conserved in worms, flies, plants, fungi and mammals, and has a distinctive structure, which includes a helicase domain and dualRNase III motifs.