Gene Therapy of Cochlear Deafness
Present Concepts and Future Aspects
Editor(s): Ryan, A.F. (La Jolla, CA)
Therapeutic Regulation of Gene Expression in the Inner Ear using RNA InterferenceMaeda Y.a · Sheffield A.M.b · Smith R.J.H.a–caMolecular Otolaryngology Research Laboratories, Department of Otolaryngology, Head and Neck Surgery, bMedical Scientist Training Program, and cInterdepartmental PhD Genetics Program, University of Iowa, Iowa City, Iowa, USA
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Article / Publication Details
Published online: June 02, 2009
Cover Date: 2009
Number of Print Pages: 24
Number of Figures: 0
Number of Tables: 0
ISBN: 978-3-8055-9035-8 (Print)
eISBN: 978-3-8055-9036-5 (Online)
Abstract
Targeting and downregulating specific genes with antisense and decoy oligonucleotides, ribozymes or RNA interference (RNAi) offer the theoretical potential of altering a disease phenotype. Here we review the molecular mechanism behind the in vivo application of RNAi-mediated gene silencing, focusing on its application to the inner ear. RNAi is a physiological phenomenon in which small, double-stranded RNA molecules (small interfering RNA, siRNA) reduce expression of homologous genes. Notable for its exquisite sequence specificity, it is ideally applied to diseases caused by a gain-of-function mechanism of action. Types of deafness in which gain-of-function mutations are observed include DFNA2 (KCNQ4), DFNA3 (GJB2) and DFNA5 (DFNA5). Several strategies can be used to deliver siRNA into the inner ear, including cationic liposomes, adeno-associated and lentiviral vectors, and adenoviral vectors. Transduction efficiency with cationic liposomes is low and the effect is transient; with adeno-associated and lentiviral vectors, long-term transfection is possible using a small hairpin RNA expression cassette.
© 2009 S. Karger AG, Basel
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Article / Publication Details
Published online: June 02, 2009
Cover Date: 2009
Number of Print Pages: 24
Number of Figures: 0
Number of Tables: 0
ISBN: 978-3-8055-9035-8 (Print)
eISBN: 978-3-8055-9036-5 (Online)
Copyright / Drug Dosage / Disclaimer
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.
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