D-RNAi-Based Therapeutics

Lin, Shi-Lung; Ying, Shao‐Yao

doi:10.1007/0-387-23695-3_13

Cited by 2 publications

(3 citation statements)

References 64 publications

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“…As shown in Figure 4D-4G, experimental results demonstrated that the miRNAs derived from a long RNA-DNA hybrid construct (≥ 150 bp) were inhibited ß-catenin gene expression in the liver and skin of developing chicken embryos. This mimics the mechanism by which interaction between the intronic miRNA precursor and genomic DNA produce a specific gene silencing effect (22,23,51). We have demonstrated that the [P 32 ]-labeled DNA component of a long RNA-DNA duplex construct in cell nuclear lysates was intact during the effective period of miRNA-induced RNA interference (RNAi), while the labeled RNA was replaced by cold homologues and excised into small 18~27-nt RNA fragments in a 3-day incubation period (22).…”

Section: Intronic Pirna-mediated Rna Interference In Chickenmentioning

confidence: 94%

“…Natural siRNAs, however, were mainly found in plants and primitive animals (worms and flies), but rarely in mammals (10). Because miRNAs are widely detected in eukaryotes, they have recently been extensively utilized in designing novel therapeutics against cancer and viral infections (22,23). Indeed, gene silencing mechanisms involving miRNAs are probably an intracellular defense system for eliminating undesired transgenes and foreign RNAs, such as retrotransposons and viruses.…”

Section: Introductionmentioning

confidence: 99%

“…The intron-derived miRNA system is activated in a specific cell type under the control of a type-II RNA polymerase (Pol-II)-directed transcriptional machinery. To overcome the Pol-III-mediated siRNA side-effects, we have successfully developed a novel Pol-II-based miRNA biogenesis strategy, employing intronic miRNA molecules (2) to knock down more than 85% of selected oncogene function or viral genome replication (22,23,47). Because of its flexibility in binding with partially complementary mRNA targets, miRNA can serve as an anti-cancer drug or vaccine, a potential major breakthrough in the treatment of cancer polymorphisms and viral mutations.…”

Section: Man-made Intronic Micrornamentioning

confidence: 99%

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Intron-mediated RNA interference and microRNA (miRNA)

Lin¹

2008

Front Biosci

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MicroRNAs (miRNAs) are small single-stranded regulatory RNAs capable of interfering with messenger RNAs (mRNAs) through complete or partial complementarities. Partial complementarity gives miRNAs a flexibility which is useful for construction of new therapies against cancer polymorphisms and viral mutations. Varieties of miRNAs have been reported in diverse species; and they are believed to induce RNA interference (RNAi), a post-transcriptional gene silencing mechanism. Recently, many intronic sequences have been shown to encode microRNAs. Intronic miRNA, a new class of miRNAs, is derived from introns by RNA splicing and Dicer processing, and it differs uniquely from previously described intergenic miRNA in that intronic miRNAs require type II RNA polymerases (Pol-II) and spliceosomal components for their biogenesis. Several kinds of intronic miRNAs have been identified; however, their functions and applications have not been reported. Here, we show for the first time that intron-derived miRNAs are able to induce RNA interference in many cells demonstrating the evolutionary preservation of this post-transcriptional regulatory system in vivo.

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Section: Intronic Pirna-mediated Rna Interference In Chickenmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Man-made Intronic Micrornamentioning

confidence: 99%

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Intron-mediated RNA interference and microRNA (miRNA)

Lin¹

2008

Front Biosci

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Intron-Mediated RNA Interference and microRNA Biogenesis

Ying

Lin

2008

Methods in Molecular Biology

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Nearly 97% of the human genome is non-coding DNA, and introns occupy most of it around the gene-coding regions. Numerous intronic sequences have been recently found to encode microRNAs, which are responsible for RNA-mediated gene silencing through RNA interference (RNAi)-like pathways. microRNAs (miRNAs), small single-stranded regulatory RNAs capable of interfering with intracellular messenger RNAs (mRNAs) that contain either complete or partial complementarity, are useful for the design of new therapies against cancer polymorphism and viral mutation. This flexible characteristic is different from double-stranded siRNAs (small interfering RNAs) because a much more rigid complementarity is required for siRNA-induced RNAi gene silencing. miRNAs were firstly discovered in Caenorhabditis elegans as native RNA fragments that modulate a wide range of genetic regulatory pathways during embryonic development. Currently, varieties of miRNAs are widely reported in plants, animals and even microbes. Intronic microRNA is a new class of miRNAs derived from the processing of gene introns. The intronic miRNAs differ uniquely from previously described intergenic miRNAs in the requirement of type II RNA polymerases (Pol-II) and spliceosomal components for their biogenesis. Several kinds of intronic miRNAs have been identified in C. elegans, mouse and human cells; however, neither function nor application has been reported. Here, we show for the first time that intron-derived miRNAs are able to induce RNA interference in not only human and mouse cells but also zebrafishes, chicken embryos and adult mice, demonstrating the evolutionary preservation of the intron-mediated gene silencing through miRNA functionality in cell and in vivo. These findings suggest an intracellular miRNA-mediated gene regulatory system, fine-tuning the degradation of protein-coding messenger RNAs.

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D-RNAi-Based Therapeutics

Cited by 2 publications

References 64 publications

Intron-mediated RNA interference and microRNA (miRNA)

Intron-mediated RNA interference and microRNA (miRNA)

Intron-Mediated RNA Interference and microRNA Biogenesis

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