GENE THERAPY - DEVELOPMENTS AND FUTURE PERSPECTIVES Edited by Chunsheng Kang Gene Therapy - Developments and Future Perspectives Edited by Chunsheng Kang Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access articles distributed under the Creative Commons Non Commercial Share Alike Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published articles. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Romina Krebel Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright Anteromite, 2010. Used under license from Shutterstock.com First published July, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Gene Therapy - Developments and Future Perspectives, Edited by Chunsheng Kang p. cm. ISBN 978-953-307-617-1 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Approach of Gene Therapy 1 Chapter 1 New Vectors for Stable and Safe Gene Modification 3 Francisco Martín, Karim Benabdellah, Marién Cobo, Pilar Muñoz, Per Anderson and Miguel G. Toscano Chapter 2 Gene Therapy Using RNAi 31 Yu-Lin Yang, Wen-Teng Chang and Yuan-Wei Shih Chapter 3 Scalable Technology to Produce Pharmaceutical Grade Plasmid DNA for Gene Therapy 53 Odalys Ruiz Hernández, Miladys Limonta Fernández, Jorge Valdes Hernández, Martha Pupo Peña and Eduardo Martínez Díaz Chapter 4 Small Interfering RNAs: Heralding a New Era in Gene Therapy 71 Maro Bujak, Ivana Ratkaj, Mirela Baus Loncar, Radan Spaventi and Sandra Kraljevic Pavelic Chapter 5 MicroRNAs in Disease and Health: Diagnostic and Therapeutic Potentials 93 Mohammad Reza Noori-Daloii and Azim Nejatizadeh Chapter 6 Gene Therapy Strategies Incorporating Large Transgenes 121 Jennifer Johnston, Christopher B. Doering and H. Trent Spencer Part 2 Evaluation of Gene Therapy 143 Chapter 7 Recent Advances and Improvements in the Biosafety of Gene Therapy 145 Jaichandran Sivalingam and Oi Lian Kon VI Contents Chapter 8 Impacts of DNA Microarray Technology in Gene Therapy 189 Yadollah Omidi, Amir Ata Saei and Jaleh Barar Chapter 9 Hopes and Disillusions in Therapeutic Targeting of Intercellular Communication in Cancer 217 Mustapha Kandouz Chapter 10 Promising Role of Engineered Gene Circuits in Gene Therapy 233 Wei-dong Wang and Jinyi Lang Chapter 11 Comparison of DNA Delivery and Expression Using Frequently Used Delivery Methods 247 Sara A. Collins, David Morrissey, Simon Rajendran, Garrett Casey, Martina F. Scallan, Patrick T. Harrison, Gerald C. O’Sullivan and Mark Tangney Part 3 Potential Applications of Gene Therapy in Future 265 Chapter 12 Preclinical and Clinical Aspects of Gene Therapy in Myocardial Infarction 267 Saurabh Bharti, Ashok Kumar Sharma, Bhaskar Krishnamurthy and Dharamvir Singh Arya Chapter 13 Gene Therapy for Therapeutic Angiogenesis 289 Rudolf Kirchmair Chapter 14 Cancer Gene Therapy - Developments and Future Perspectives 299 David A Good, Wei Duan, Jozef Anné and Ming Q Wei Chapter 15 Differential Gene Expression and Its Possible Therapeutic Implications 315 Safdar Ali and Sher Ali Chapter 16 Engineered Drug Resistant Cell-Mediated Immunotherapy 335 Anindya Dasgupta and H. Trent Spencer Preface We are delighted to be offered the opportunity to help construct a book dealing with important issues of development and future perspectives in gene therapy. The goal of our work on this project is to provide a means, via the contributions of many collaborating authors, to make our doctors become comfortable with the com- mon problems of gene therapy in a single accessible book. The current volume aims at providing an up-to-date report on the field of the devel- opment and future perspectives in gene therapy. Contributions consist of basic and translational research, as well as clinical experiences, and they outline functional mechanisms, predictive approaches, patient-related studies, and upcoming challenges in this stimulating but also controversial field of gene therapy research. We hope that our efforts and those of our collaborators will well present our specialty and may, perhaps, inspire others to delve a bit more deeply into a topic of interest. Dr. Chunsheng Kang Professor at Lab of Neuro-oncology Tianjin Neurological Institute China [...]... environmental conditions The expression of the transgene in non-target cells as well as the expression of non-physiological transgene levels may cause toxic or deleterious effects 4 Gene Therapy - Developments and Future Perspectives Therefore, an important safety issue concerning gene therapy is to achieve regulated and/ or physiological expression of the transgene(reviewed in Toscano et al 2011) Genotoxicity... Approach of Gene Therapy 1 New Vectors for Stable and Safe Gene Modification Francisco Martín, Karim Benabdellah, Marién Cobo, Pilar Muñoz, Per Anderson and Miguel G Toscano Andalusian Stem Cell Bank, Granada University, Spain 1 Introduction Stable gene modification without affecting normal cellular function is a main goal both for basic and applied science Current strategies to achieve stable gene modification... sites and regulatory gene regions Modlich et al found(Modlich et al., 2009) that the LVs insertion New Vectors for Stable and Safe Gene Modification 5 Fig 1 Main strategies to achieve safer stable genetic modification for gene therapy applications First generation gammaretroviral vectors (top) contained strong enhancer sequences in their LTR backbones that can influence genes located upstream (Gene. .. meganucleases together with the correct version of the gene 6 Gene Therapy - Developments and Future Perspectives pattern was approximately threefold less likely than the GVs to trigger transformation of primary hematopoietic cells 4- The LVs backbone is more flexible to modifications and insertions Of all LVs, HIV-1-based are by far the most used for gene therapy strategies Other lentiviruses commonly used... recognizes two sequences flanking the transposon Any sequence included between the two flanking regions can also be mobilized and this characteristic makes the transposons attractive as a gene therapy tools 12 Gene Therapy - Developments and Future Perspectives to achieve stable transgene integrations (Figure 4) The mechanism involved behind the mobilization of transposons is described elsewhere(Izsvak... in vector expression such as transcriptional silencing Therefore a main goal of gene therapists has been to isolate integrative vectors from the host chromatin in such a way that 1- enhancers present in the 10 Gene Therapy - Developments and Future Perspectives vector can not influence expression of cellular host genes and 2- that regulatory sequences present in the host chromatin can not influence... (ITRs) and trans- (Rep68/78) acting components of AAV viruses to specifically target transgenes into the AAVS1 integration site at 14 Gene Therapy - Developments and Future Perspectives chromosome 19 This technology has opened the possibility of integrating large DNA sequences in a site specific fashion with the aim of minimizing genotoxicity AAV-Hybrid vectors based on plasmids, baculovirus, Ad and HSV... transgene expression in liver(Olivares et al., 2002) and retina(Chalberg et al., 2005) Fig 6 Site specific integration of phiC31 integrase in the human genome PhiC31 integrase mediates the integration of a plasmid containing an attB site and the transgene into pseudoattP sites at the human genome Once integrated the donor sequence is flanked by attR and attL sequences 18 Gene Therapy - Developments and. .. (ClinicalTrials.gov Identifier: NCT00842634 and NCT01044654) 6 Conclusion Stable gene modification without affecting normal cellular function is a main goal both for basic and applied science Most gene therapy targets, such as inherited, infectious and degenerative diseases will benefit from a safe and efficient integrative system Old strategies to achieve stable gene medication are either very inefficient... reduce viral titer in a promoterdependent manner Hum Gene Ther 19,8, (Aug), 840-850, ISSN:1557-7422 (Electronic)1043-0342 (Linking) 24 Gene Therapy - Developments and Future Perspectives Hanawa, H., Hematti, P., Keyvanfar, K., Metzger, M.E., Krouse, A., Donahue, R.E., Kepes, S., Gray, J., Dunbar, C.E., Persons, D.A., and Nienhuis, A.W (2004) Efficient gene transfer into rhesus repopulating hematopoietic . GENE THERAPY - DEVELOPMENTS AND FUTURE PERSPECTIVES Edited by Chunsheng Kang Gene Therapy - Developments and Future Perspectives Edited by. Bhaskar Krishnamurthy and Dharamvir Singh Arya Chapter 13 Gene Therapy for Therapeutic Angiogenesis 289 Rudolf Kirchmair Chapter 14 Cancer Gene Therapy - Developments and Future Perspectives 299. Christopher B. Doering and H. Trent Spencer Part 2 Evaluation of Gene Therapy 143 Chapter 7 Recent Advances and Improvements in the Biosafety of Gene Therapy 145 Jaichandran Sivalingam and Oi Lian Kon