NON-VIRAL GENE THERAPY Edited by Xu-bo Yuan Non-Viral Gene Therapy Edited by Xu-bo Yuan Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons 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. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice 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 chapters. 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 Sashkin, 2011. Used under license from Shutterstock.com First published October, 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 Non-Viral Gene Therapy, Edited by Xu-bo Yuan p. cm. ISBN 978-953-307-538-9 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Chapter 1 Non-Viral Gene Therapy Vectors Carrying Genomic Constructs 1 George Kotzamanis, Hassan Abdulrazzak, Athanassios Kotsinas and Vassilis G. Gorgoulis Chapter 2 Non-Viral Delivery Systems in Gene Therapy and Vaccine Development 27 Azam Bolhassani and Sima Rafati Chapter 3 Gene Delivery Systems: Tailoring Vectors to Reach Specific Tissues 51 Carlos J. Alméciga-Díaz, Rocio Cuaspa and Luis A. Barrera Chapter 4 Investigation of Transfection Barriers Involved in Non-Viral Nanoparticulate Gene Delivery in Different Cell Lines 77 Stefanie Häfele and Regine Süss Chapter 5 The Mechanical Agitation Method of Gene Transfer for Ex-Vivo Gene Therapy 91 Hea-Jong Chung, Hyun-Seo Lee, Hyeon-Jin Kim and Seong-Tshool Hong Chapter 6 Gene Therapy of Some Genetic Diseases by Transferring Normal Human Genomic DNA into Somatic Cells and Stem Cells from Patients 105 Liting Song Chapter 7 Non Viral Gene Transfer Approaches for Lysosomal Storage Disorders 147 Ursula Matte, Guilherme Baldo and Roberto Giugliani Chapter 8 DNA Vaccination by Electrogene Transfer 169 Pieranna Chiarella, Vito Michele Fazio and Emanuela Signori VI Contents Chapter 9 Gene Delivery with Ultrasound and Microbubbles 199 Evan Unger and Terry Matsunaga Chapter 10 Ultrasound-Mediated Gene Delivery 213 Carol H. Miao and Andrew A. Brayman Chapter 11 Polyamine – Lipid Conjugates as Effective Gene Carriers: Chemical Structure, Morphology, and Gene Transfer Activity 243 Takehisa Dewa, Tomohiro Asai, Naoto Oku and Mamoru Nango Chapter 12 Technological Aspects of Scalable Processes for the Production of Functional Liposomes for Gene Therapy 267 Julia E. Trevisan, Leide P. Cavalcanti, Cristiano L. P. Oliveira, Lucimara G. de La Torre and Maria Helena A. Santana Chapter 13 Cationic Liposomes in Different Structural Levels for Gene Delivery 293 Yinan Zhao, Defu Zhi and Shubiao Zhang Chapter 14 Neutral Liposomes and DNA Transfection 319 Michela Pisani, Giovanna Mobbili and Paolo Bruni Chapter 15 Non-Viral Gene Delivery Systems Based on Cholesterol Cationic Lipids: Structure-Activity Relationships 349 Michael A. Maslov and Marina A. Zenkova Chapter 16 Polycation-Mediated Gene Delivery: The Physicochemical Aspects Governing the Process 381 Manuel Alatorre-Meda, Eustolia Rodríguez-Velázquez and Julio R. Rodríguez Chapter 17 Medical Polymer-Based Gene Therapy 417 Hu-Lin Jiang, You-Kyoung Kim, Chong-Su Cho and Myung-Haing Cho Chapter 18 Chitosan and Its Modifications: Are They Possible Vehicles for Gene Therapy? 439 Ureporn Kedjarune-Leggat and Peter A. Leggat Chapter 19 Chitosan-DNA/siRNA Nanoparticles for Gene Therapy 455 Qin Shi, Marcio J. Tiera, Xiaoling Zhang, Kerong Dai, Mohamed Benderdour and Julio C. Fernandes Chapter 20 Toxicity of Polymeric-Based Non-Viral Vector Systems for Pulmonary siRNA Application 481 Andrea Beyerle, Thomas Kissel and Tobias Stoeger Contents VII Chapter 21 PAMAM Dendrimer as Potential Delivery System for Combined Chemotherapeutic and MicroRNA-21 Gene Therapy 499 Xuan Zhou, Yu Ren, Xubo Yuan, Peiyu Pu and Chunsheng Kang Chapter 22 Nanomedicine Based Approaches to Cancer Diagonsis and Therapy 515 Roderick A. Slavcev, Shawn Wettig and Tranum Kaur Chapter 23 Toxicogenomics of Nonviral Cationic Gene Delivery Nanosystems 547 Yadollah Omidi, Vala Kafil and Jaleh Barar Chapter 24 Nano-Particulate Calcium Phosphate as a Gene Delivery System 577 Babak Mostaghaci, Arash Hanifi, Brigitta Loretz and Claus-Michael Lehr Chapter 25 Modular Multifunctional Protein Vectors for Gene Therapy 597 Hugo Peluffo Chapter 26 Peptides as Promising Non-Viral Vectors for Gene Therapy 615 Wei Yang Seow and Andrew JT George Chapter 27 Binding of Protein-Functionalized Entities onto Synthetic Vesicles 645 Federica De Persiis, Ramon Pons, Carlotta Pucci, Franco Tardani and Camillo La Mesa Chapter 28 Targeting TRAIL Receptors with Genetically- Engineered CD34+ Hematopoietic Stem Cells 661 Carmelo Carlo-Stella, Arianna Giacomini, Silvia L. Locatelli, Cristiana Lavazza and Alessandro M. Gianni Chapter 29 Pyrrole-Imidazole Polyamides for Gene Therapy: Bioanalytical Methods and Pharmacokinetics 679 Tomonori Kamei, Takahiko Aoyama, Takahiro Ueno, Noboru Fukuda, Hiroki Nagase and Yoshiaki Matsumoto Preface Gene therapy provides great promises for cancer treatment. Two essential components are absolutely necessary in current gene therapy: an effective therapeutic gene that can be expressed at a target site, and an efficient and safe delivery system. This book aims to provide an up-to-date report in gene delivery research. With the multidisciplinary contribution in gene delivery, the book covers: (1) various gene delivery systems, like cationic lipids, cationic polymers and silica nanoparticles; (2) methods to enhance delivery, such as ultrasound and microbubble; (3) materials with modification and multifunction for the tumor or tissue targeting. The book provides an introductory text for nonspecialists in gene delivery, and prepares readers to perform well-controlled experiments with appropriate controls. It illustrates ideas and models with more than 100 figures, including 64 photomicrographs. Many specialists are not familiar with both drug delivery and the molecular biology of DNA vectors. In this book, molecular biologists will gain a basic knowledge of lipids, liposome, and other gene delivery vehicles and lipids, while drug delivery scientists will better understand DNA, molecular biology, and DNA manipulation. We acknowledge our contributors and section editors for generously sharing their expertise and scientific skills. W e hope this book can help the researchers come up with new ideas and finally bring the gene therapy approaches to the clinical trials. Xu-bo Yuan Tianjin University China [...]... as a method for high-level nonviral gene transfer to the lung Gene therapy, 10(18), pp 1608-15 Dorin, JR., Farley, R, Webb, S., Smith, SN., Farini, E., Delaney, SJ., Wainwright, B., Alton, EW & Porteous, DJ (1996) A demonstration using mouse models that successful 20 Non-Viral Gene Therapy gene therapy for cystic fibrosis requires only partial gene correction Gene therapy, 3(9), pp 797-801 Eastman,... genomic CFTR-locus containing BAC (see section 3) 8 Conclusion Non-viral gene therapy using the entire genomic locus of the therapeutic gene has two advantages over viral cDNA gene therapy; it is not associated with unwanted immune responses and can confer controlled levels of transgene expression in correct time and 18 Non-Viral Gene Therapy tissue When combined with a system for extra-chromosomal... Using magnetic forces to enhance non-viral gene transfer to airway epithelium in vivo Gene therapy, 13(21), pp 1545-52 Xenariou, Stefania, Liang, H.-D., Griesenbach, Uta, Zhu, J., Farley, Raymond, Somerton, L., et al (2010) Low-frequency ultrasound increases non-viral gene transfer to the mouse lung Acta biochimica et biophysica Sinica, 42(1), pp 45-51 26 Non-Viral Gene Therapy Xing, L., Salas, M., Lin,... controlled and tissue-specific expression of a gene usually lie within the introns and the sequences before and after the gene Therefore, the use of genomic constructs which contain the introns and flanking DNA of the therapeutic gene is expected to be more effective than that of minigene constructs in gene therapy for certain genetic diseases where precise levels of the gene product are required (reviewed by... genomic constructs rather than cDNA in gene therapy is that they contain all the introns and flanking DNA which can confer full control of gene expression Non-Viral Gene Therapy Vectors Carrying Genomic Constructs 3 Inclusion of introns also allows correct function of genes that encode for different products through differential splicing, such as the immunoglobulin genes Promoters that lie in the flanking... efficient than other non-viral gene delivery methods such as electroporation and hydrodynamic injection (Magin-Lachmann et al., 2004) 3.3 Ex vivo delivery to cells An alternative to in vivo delivery of DNA for gene therapy is the ex vivo approach This procedure consists of surgically removing target cells from a patient, transducing them with 8 Non-Viral Gene Therapy an appropriate therapeutic gene in culture... Regardless of the type and size of the therapeutic gene (small cDNA versus large genomic DNA) and the delivery method (viral versus non-viral) to be used in a gene therapy protocol, efficient retention and long-term expression of the transgene is required so as to eliminate the need for re-administrations Integration into the host genome has widely been used in gene therapy to fulfil this requirement However,... only a large array of α- Non-Viral Gene Therapy Vectors Carrying Genomic Constructs 11 satellite (alphoid) DNA and some marker genes into HT1080 cells No telomeric sequences or an origin of replication have been shown to be required, probably due to generation of circular HACs and initiation of replication at origins found within the marker genes (Ebersole et al., 2000) HACs generated this way exist... and far from known oncogenes (Chalberg et al., 2005) A series of studies have validated the potential of ΦC31 integrase-based vector systems in ex vivo gene therapy by demonstrating expression of different therapeutic genes in cultured cells including human embryonic stem cells (Thyagarajan et al., 2008) and in in vivo gene therapy by showing expression of different therapeutic genes in animal models,... insertional mutagenesis in a gene therapy application In addition, persistent expression of the viral Rep protein is toxic and can cause chromosome instability and mobilisation of the transgene (McCarty et al., 2004) 6 Methods for modification of large DNA molecules Gene therapy using genomic constructs entails engineering of large DNA fragments often of repetitive nature For instance, marker genes and other . NON-VIRAL GENE THERAPY Edited by Xu-bo Yuan Non-Viral Gene Therapy Edited by Xu-bo Yuan Published by InTech. constructs rather than cDNA in gene therapy is that they contain all the introns and flanking DNA which can confer full control of gene expression. Non-Viral Gene Therapy Vectors Carrying Genomic. Chapter 25 Modular Multifunctional Protein Vectors for Gene Therapy 597 Hugo Peluffo Chapter 26 Peptides as Promising Non-Viral Vectors for Gene Therapy 615 Wei Yang Seow and Andrew JT George Chapter