Targeting long non-coding RNA to therapeutically upregulate gene expression

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Claes Wahlestedt
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[1] University of Miami Miller School of Medicine,Center for Therapeutic Innovation and the Department of Psychiatry and Behavioral Sciences
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The human genome is pervasively transcribed. Most RNA transcripts represent non-coding RNAs (ncRNAs), of which there are many categories. This article focuses on long non-coding RNAs (lncRNAs).Many lncRNAs have been shown to be functional and/or related to several human diseases, including various forms of cancer and inheritable diseases such as Huntington's disease and Fragile X syndrome. lncRNAs can positively or negatively regulate gene expression and chromatin architecture.Natural antisense transcripts (NATs) are highly abundant in the human genome and found in many known gene loci where they are transcribed in the opposite direction of conventional protein-coding genes.NATs frequently regulate the expression of protein-coding genes, either positively or negatively. Most NATs mediate transcriptional repression at the chromatin level.AntagoNATs are oligonucleotides that specifically target NATs and are capable of upregulating the expression of corresponding protein coding genes in vitro as well as in vivo.AntagoNATs induce gene upregulation in a gene-locus-specific and reversible manner.AntagoNAT upregulation technology has been applied to the upregulation of genes including growth factors, tumour suppressors, transcription factors and those genes that are deficient in genetic diseases.There is a scarcity of other methods for inducing locus-specific and reversible gene upregulation.
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页码:433 / 446
页数:13
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