Antisense strategies in neurobiology

Weiss, Benjamin; Davidkova, Genoveva; Zhang, Sui‐Po

doi:10.1016/s0197-0186(96)00105-2

Cited by 63 publications

(27 citation statements)

References 136 publications

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“…The use of antisense, targeted to transcripts encoding biologically active proteins, provides a novel and highly selective means to understand the function of native proteins (64). Among the various antisense strategies available, the most specific and widely used have been shown to be antisense oligodeoxynucleotides (ASO) and antisense RNA (64). Our results show that both antisense strategies significantly inhibited native ClC-3 protein, VSOAC currents, and RVD.…”

Section: Discussionmentioning

confidence: 68%

“…Antisense (oligonucleotides or cRNA) has become a highly specific and effective way to inhibit protein translation in vivo (62,63). The use of antisense, targeted to transcripts encoding biologically active proteins, provides a novel and highly selective means to understand the function of native proteins (64). Among the various antisense strategies available, the most specific and widely used have been shown to be antisense oligodeoxynucleotides (ASO) and antisense RNA (64).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

ClC-3 Is a Fundamental Molecular Component of Volume-sensitive Outwardly Rectifying Cl− Channels and Volume Regulation in HeLa Cells and Xenopus laevis Oocytes

Hermoso

Satterwhite²,

Andrade

et al. 2002

Journal of Biological Chemistry

106

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

ClC-3 Is a Fundamental Molecular Component of Volume-sensitive Outwardly Rectifying Cl− Channels and Volume Regulation in HeLa Cells and Xenopus laevis Oocytes

Hermoso

Satterwhite²,

Andrade

et al. 2002

Journal of Biological Chemistry

106

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“…There is a concomitant decrease in MBP RNA transport, providing further evidence that A2RE-mediated transport is hnRNP A2-dependent. Although some artifacts are possible with antisense protocols (35), they predominantly involve sense effects or nonspecific effects of exposure to oligonucleotides. At the concentrations used here, treatment with the sense oligonucleotide had no detectable effect on RNA transport, and neither oligonucleotide had obvious toxicity affecting myelin membrane morphology or oligodendrocyte size.…”

Section: Figmentioning

confidence: 99%

Mutational Analysis of a Heterogeneous Nuclear Ribonucleoprotein A2 Response Element for RNA Trafficking

Munro

Magee

Kidd

et al. 1999

Journal of Biological Chemistry

182

210

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Cytoplasmic transport and localization of mRNA has been reported for a range of oocytes and somatic cells. The heterogeneous nuclear ribonucleoprotein (hnRNP) A2 response element (A2RE) is a 21-nucleotide segment of the myelin basic protein mRNA that is necessary and sufficient for cytoplasmic transport of this message in oligodendrocytes. The predominant A2RE-binding protein in rat brain has previously been identified as hnRNP A2. Here we report that an 11-nucleotide subsegment of the A2RE (A2RE11) was as effective as the fulllength A2RE in binding hnRNP A2 and mediating transport of heterologous RNA in oligodendrocytes. Point mutations of the A2RE11 that eliminated binding to hnRNP A2 also markedly reduced the ability of these oligoribonucleotides to support RNA transport. Oligodendrocytes treated with antisense oligonucleotides directed against the translation start site of hnRNP A2 had reduced levels of this protein and disrupted transport of microinjected myelin basic protein RNA. Several A2RE-like sequences from localized neuronal RNAs also bound hnRNP A2 and promoted RNA transport in oligodendrocytes. These data demonstrate the specificity of A2RE recognition by hnRNP A2, provide direct evidence for the involvement of hnRNP A2 in cytoplasmic RNA transport, and suggest that this protein may interact with a wide variety of localized messages that possess A2RE-like sequences.Vectorial transport and localized translation of mRNA in the cytoplasm affords a mechanism for establishing an asymmetric distribution of cytosolic proteins in cells. This is particularly important in oogenesis and embryonic development (1-8). In somatic cells, some mRNAs are also transported to discrete locations within the cell. These include myelin basic protein (MBP) 1 mRNA, which is localized in the myelinating periphery of oligodendrocytes (9 -11), microtubule-associated protein 2A (MAP2A) and tau, which are localized in neurites (12-14), and ␤-actin mRNA, which is localized in the leading edge of fibroblasts (15-17). An active, multistep, cytoplasmic transport pathway has been delineated for MBP mRNA in cultured oligodendrocytes. MBP transcripts microinjected into the soma assemble into granules that move out along the myelin-forming processes (18,19). Transport of these granules is dependent on the presence of kinesin and intact microtubules (20). Similar RNA-rich granules have been observed in other cells (21)(22)(23)(24).A cis-acting sequence sufficient and necessary for MBP mRNA transport has been identified within a 21-nucleotide stretch of the 3Ј-untranslated region. Incorporation of this segment, the hnRNP A2 response element (A2RE, formerly termed the RNA transport sequence (25)), into heterologous RNAs mediates transport into the processes and also enhances translation.2 A2RE-like sequences are present in other localized mRNAs including mouse MAP2A, mouse protamine 2, and rat glial fibrillary acidic protein (25), suggesting that the A2RE represents a general signal for RNA transport.Earlier we used biotin-labeled oligorib...

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“…As reviewed elsewhere [21], several characteristics make antisense compounds more attractive than conventional pharmacological antagonists for inhibiting the function of specific proteins. Antisense DNA and RNA have extremely high specificity for their target, a degree of specificity which cannot ordinarily be achieved using conventional pharmacological antagonists.…”

Section: Advantages Of Antisense Approaches Over Conventional Pharmacmentioning

confidence: 99%

Antisense RNA gene therapy for studying and modulating biological processes

Weiss¹,

Davidkova²,

Zhou³

1999

Cellular and Molecular Life Sciences (CMLS)

103

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Agents that produce their effects through an antisense mechanism offer the possibility of developing highly specific alternatives to traditional pharmacological antagonists, thereby providing a novel class of therapeutic agents, ones which act at the level of gene expression. Among the antisense compounds, antisense RNA produced intracellularly by an expression vector has been used extensively in the past several years. This review considers the advantages of the antisense RNA approach over the use of antisense oligodeoxynucleotides, the different means by which one may deliver and produce antisense RNA inside cells, and the experimental criteria one should use to ascertain whether the antisense RNA is acting through a true antisense mechanism. Its major emphasis is on exploring the potential therapeutic use of antisense RNA in several areas of medicine. For example, in the field of oncology antisense RNA has been used to inhibit several different target proteins, such as growth factors, growth factor receptors, proteins responsible for the invasive potential of tumor cells and proteins directly involved in cell cycle progression. In particular, a detailed discussion is presented on the possibility of selectively inhibiting the growth of tumor cells by using antisense RNA expression vectors directed to the individual calmodulin transcripts. Detailed consideration is also provided on the development and potential therapeutic applications of antisense RNA vectors targeted to the D2 dopamine receptor subtype. Studies are also summarized in which antisense RNA has been used to develop more effective therapies for infections with certain viruses such as the human immunodeficiency virus and the virus of hepatitis B, and data are reviewed suggesting new approaches to reduce elevated blood pressure using antisense RNA directed to proteins and receptors from the renin-angiotensin system. Finally, we outline some of the problems which the studies so far have yielded and some outstanding questions which remain to be answered in order to develop further antisense RNA vectors as therapeutic agents.

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Antisense strategies in neurobiology

Cited by 63 publications

References 136 publications

ClC-3 Is a Fundamental Molecular Component of Volume-sensitive Outwardly Rectifying Cl− Channels and Volume Regulation in HeLa Cells and Xenopus laevis Oocytes

ClC-3 Is a Fundamental Molecular Component of Volume-sensitive Outwardly Rectifying Cl− Channels and Volume Regulation in HeLa Cells and Xenopus laevis Oocytes

Mutational Analysis of a Heterogeneous Nuclear Ribonucleoprotein A2 Response Element for RNA Trafficking

Antisense RNA gene therapy for studying and modulating biological processes

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