Antisense Oligonucleotides

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Abstract

Antisense technology was developed to inhibit gene expression by utilizing an oligonucleotide complementary to the mRNA which encodes the target gene. There are a few possible mechanisms for the inhibitory effects of antisense oligonucleotides. Among them, degradation of mRNA by RNase H is considered to be the major mechanism of action for antisense oligonucleotides. This technique was originally used to elucidate the function of a target gene, but may also have therapeutic applications, provided it is designed carefully and properly.

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Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate the signal for T-cell proliferation.

Deborah Nelson, Jerry P. Greenberg, Christopher J. Lord (1994)

The interleukin-2 receptor (IL-2R) consists of three distinct chains (alpha, beta, gamma) which bind IL-2 and generate a proliferative signal in T cells. To define the mechanism of receptor activation, chimaeric receptors were constructed from the intracellular region of either IL-2R beta or IL-2R gamma and the extracellular region of c-kit, a receptor tyrosine kinase that homodimerizes on binding stem cell factor (SCF). We report here that binding of SCF to the beta-chain chimaera induced proliferation of the pro-B-cell line BA/F3, but not T cells. But in T cells expressing both the beta- and gamma-chain chimaeras, SCF induced proliferation and tyrosine phosphorylation characteristic of the native IL-2R signal. Chimaeric IL-2 receptor beta and gamma chains constructed with the heterodimeric extracellular regions of the granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) also provided the IL-2R signal. Thus, heterodimerization of the cytoplasmic domains of IL-2R beta and -gamma appears necessary and sufficient for signalling in T cells.

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Efficient gene transfer with less cytotoxicity by means of cationic multilamellar liposomes.

K Yagi, H Noda, M Kurono … (1993)

A simple procedure for the preparation of cationic multilamellar vesicles (MLV) consisting of N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride, dilauroyl phosphatidylcholine, and dioleoyl phosphatidylethanolamine in a molar ratio of 1:2:2 was devised. When bacteriophage lambda DNA was encapsulated into these liposomes, entrapment efficiency was found to be nearly 100%, and digestibility of the DNA was less than 10%. Upon encapsulation of the plasmid pCH110 into cationic MLV, efficient expression was comparable to that obtained with cationic vesicles prepared by reverse-phase evaporation method (REV). Cytotoxicity of the present liposomes was less than that of cationic REV and far less than that of Lipofectin.

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Journal

Journal ID (publisher-id): EXN

Journal ID (nlm-ta): Nephron Exp Nephrol

Journal ID (doi): 10.1159/issn.1660-2129

Title: Cardiorenal Medicine

Publisher: S. Karger AG

ISSN (Electronic): 1660-2129

Publication date Subscription-year: 1998

Publication date (Print): February 1998

Publication date (Electronic): 04 February 1998

Volume: 6

Issue: 1

Pages: 84-88

Affiliations

Department of Medicine III, Okayama University Medical School, Okayama, Japan

Article

Publisher ID: 20509 Other ID: Exp Nephrol 1998;6:84–88

DOI: 10.1159/000020509

SO-VID: 12f23cde-1449-420b-9054-505d2ee5a914

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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Antisense Oligonucleotides

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Abstract

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Karger: Nephrology

Most cited references 2

Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate the signal for T-cell proliferation.

Efficient gene transfer with less cytotoxicity by means of cationic multilamellar liposomes.

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