For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
50
views
127
references
 Top references
cited by
34
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      659
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      RNAi Therapeutic Platforms for Lung Diseases

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          RNA interference (RNAi) is rapidly becoming an important method for analyzing gene functions in many eukaryotes and holds promise for the development of therapeutic gene silencing. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, i.e. small interfering RNAs (siRNAs) and microRNAs (miRNAs), are central to RNAi. Drug discovery studies and novel treatments of siRNAs are currently targeting a wide range of diseases, including various viral infections and cancers. Lung diseases in general are attractive targets for siRNA therapeutics because of their lethality and prevalence. In addition, the lung is anatomically accessible to therapeutic agents via the intrapulmonary route. Recently, increasing evidence indicates that miRNAs play an important role in lung abnormalities, such as inflammation and oncogenesis. Therefore, miRNAs are being targeted for therapeutic purposes. In this review, we present strategies for RNAi delivery and discuss the current state-of-the-art RNAi-based therapeutics for various lung diseases.

          Related collections

          Most cited references127

          • Record: found
          • Abstract: found
          • Article: not found

          Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis.

          Eva van Rooij, Lillian Sutherland, Jeffrey Thatcher … (2008)
          Acute myocardial infarction (MI) due to coronary artery occlusion is accompanied by a pathological remodeling response that includes hypertrophic cardiac growth and fibrosis, which impair cardiac contractility. Previously, we showed that cardiac hypertrophy and heart failure are accompanied by characteristic changes in the expression of a collection of specific microRNAs (miRNAs), which act as negative regulators of gene expression. Here, we show that MI in mice and humans also results in the dysregulation of specific miRNAs, which are similar to but distinct from those involved in hypertrophy and heart failure. Among the MI-regulated miRNAs are members of the miR-29 family, which are down-regulated in the region of the heart adjacent to the infarct. The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression. We conclude that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.
          Article 0 comments Cited 600 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Expression profiling reveals off-target gene regulation by RNAi.

            Aimee Jackson, Steven Bartz, Janell M Schelter … (2003)
            RNA interference is thought to require near-identity between the small interfering RNA (siRNA) and its cognate mRNA. Here, we used gene expression profiling to characterize the specificity of gene silencing by siRNAs in cultured human cells. Transcript profiles revealed siRNA-specific rather than target-specific signatures, including direct silencing of nontargeted genes containing as few as eleven contiguous nucleotides of identity to the siRNA. These results demonstrate that siRNAs may cross-react with targets of limited sequence similarity.
            Article 0 comments Cited 542 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice.

              Andrew H Williams, Gregorio Valdez, Viviana Moresi … (2009)
              Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of motor neurons, denervation of target muscles, muscle atrophy, and paralysis. Understanding ALS pathogenesis may require a fuller understanding of the bidirectional signaling between motor neurons and skeletal muscle fibers at neuromuscular synapses. Here, we show that a key regulator of this signaling is miR-206, a skeletal muscle-specific microRNA that is dramatically induced in a mouse model of ALS. Mice that are genetically deficient in miR-206 form normal neuromuscular synapses during development, but deficiency of miR-206 in the ALS mouse model accelerates disease progression. miR-206 is required for efficient regeneration of neuromuscular synapses after acute nerve injury, which probably accounts for its salutary effects in ALS. miR-206 mediates these effects at least in part through histone deacetylase 4 and fibroblast growth factor signaling pathways. Thus, miR-206 slows ALS progression by sensing motor neuron injury and promoting the compensatory regeneration of neuromuscular synapses.
              Article 0 comments Cited 280 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Pharmaceuticals (Basel)
                Journal ID (iso-abbrev): Pharmaceuticals (Basel)
                Journal ID (publisher-id): pharmaceuticals
                Title: Pharmaceuticals
                Publisher: MDPI
                ISSN (Electronic): 1424-8247
                Publication date (Electronic): 06 February 2013
                Publication date Collection: February 2013
                Volume: 6
                Issue: 2
                Pages: 223-250
                Affiliations
                [1 ]Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, 104-0045, Japan; E-Mails: yufujit2@ 123456ncc.go.jp (Y.F.); futakesh@ 123456ncc.go.jp (F.T.)
                [2 ]Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, 105-8461, Japan; E-Mail: kkuwano@ 123456jikei.ac.jp (K.K.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: tochiya@ 123456ncc.go.jp ; Tel.: +81-3-3542-2511; Fax: +81-3-5565-0727.
                Article
                Publisher ID: pharmaceuticals-06-00223
                DOI: 10.3390/ph6020223
                PMC ID: 3816685
                PubMed ID: 24275949
                SO-VID: 5515e361-1898-4900-abf3-0ce6a14a1126
                Copyright © © 2013 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 19 December 2012
                Date revision received : 19 January 2013
                Date accepted : 01 February 2013
                Categories
                Subject: Review

                Keywords: rnai,sirna,mirna,drug delivery system,lung diseases,lung cancer
                Data availability:
                Keywords: rnai, sirna, mirna, drug delivery system, lung diseases, lung cancer

                Comments

                Comment on this article

                scite_

                Similar content659

                See all similar

                Cited by32

                See all cited by

                Most referenced authors2,460

                See all reference authors