Download or read book Investigation of Barriers to Non viral Gene Delivery and Design of Novel Polymer based Gene Delivery Systems written by Akin Akinc and published by . This book was released on 2003 with total page 252 pages. Available in PDF, EPUB and Kindle. Book excerpt: The safe and effective delivery of therapeutic genes is the most significant challenge facing gene therapy today. Viral vectors remain the dominant approach for addressing the delivery problem; however, concerns regarding the safety of viral vectors have resulted in an increasing interest in non-viral vectors. Non-viral vectors offer the promise of improved safety, but because they have yet to match the functional sophistication of viral vectors, their transfection efficiencies have lagged those of viral vectors. The rational design of functional non-viral vectors requires a thorough understanding of both the cell's sophisticated machinery and the vector material's functional properties. We have developed a novel, flow cytometry based tool for investigating both the cellular uptake and lysosomal trafficking of non-viral vectors, two important barriers to efficient gene transfer. Using this and other tools we investigated the gene transfer properties of polyethylenimine (PEI), a highly effective non-viral vector material. We demonstrated that the transfection efficiency of this polymer is due to its ability to avoid lysosomal degradation as a result of its buffering capacity, providing quantitative validation of the proton sponge hypothesis. By studying the gene transfer properties of a library of polymeric vectors, we were able to elucidate new vector structure-function relationships. We also investigated the combined impact of non-structural factors-such as polymer molecular weight, polymer chain end-group, and polymer/DNA ratio-on gene transfer. The findings of these studies have lead to the development of non-viral vectors with transfection efficiencies surpassing those of PEI and Lipofectamine 2000, two of the best commercially available non-viral vectors.

Download or read book Polymers and Nanomaterials for Gene Therapy written by Ravin Narain and published by Woodhead Publishing. This book was released on 2016-01-09 with total page 303 pages. Available in PDF, EPUB and Kindle. Book excerpt: Polymers and Nanomaterials for Gene Therapy provides the latest information on gene therapy, a topic that has attracted significant attention over the past two decades for the treatment of inherited and acquired genetic diseases. Major research efforts are currently focused on designing suitable carrier vectors that compact and protect oligonucleotides for gene therapy. The book explores the most recent developments in the field of polymer science and nanotechnology, and how these advancements have helped in the design of advanced materials. Non-viral vector systems, including cationic lipids, polymers, dendrimers, peptides and nanoparticles, are potential routes for compacting DNA for systemic delivery. However, unlike viral analogues that have no difficulty in overcoming cellular barriers and immune defense mechanisms, non-viral gene carriers consistently exhibit significant reduced transfection efficiency due to numerous extra- and intracellular obstacles. Therefore, biocompatibility and potential for large-scale production make these compounds increasingly attractive for gene therapy. This book contains chapters on the engineering of polymers and nanomaterials for gene therapy, and how they can form complexes with DNA and avoid both in vitro and in vivo barriers. Other chapters describe in vitro, ex vivo, in vivo gene therapy studies, and the current issues affecting non-viral gene therapy. Explores current challenges in the research of genetic diseases Discusses polymers for gene therapy and their function in designing advanced materials Provides examples of organic and inorganic nanomaterials for gene therapy Includes labeling, targeting, and assays Looks at characterization, physico-(bio)chemical properties, and applications

Download or read book An Investigation of the Barriers to Non viral Gene Delivery written by David Alan Milroy and published by . This book was released on 1999 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Converging Chemical and Cell based Approaches for Improved Non viral Gene Delivery written by Federica Ponti and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Non-viral gene delivery strategies have attracted significant interest in the development of novel therapeutic approaches as well as for basic and applied research in vitro. Compared to popular viral vectors, the class of non-viral carriers, namely cationic lipids (CLs) and polymers (CPs) able to spontaneously interact with negatively charged nucleic acids (NAs) to give nanoparticles called complexes, is now witnessing a surge of interest within the scientific community because they are relatively safe, cost-effective, and they can be easily produced and functionalized even at large scale. However, their efficiency in achieving the delivery tasks is still too low to outperform their viral counterparts. The efficacy of non-viral vectors is a tradeoff between their ability to drive NAs into cells, thus allowing/inhibiting their expression, their inherent toxicity, and their ability to deliver genes to target cells. Extensive research effort has thus been put into developing novel ways to improve the efficiency of such a class of delivery systems. In this context, my Ph.D. aimed at developing innovative strategies to improve non-viral vector effectiveness. To this purpose, we dealt with the delivery issue from two different perspectives: on one hand, the modulation of the vector chemistry was disclosed as a way to develop multifunctional carriers with improved effectiveness; on the other hand, we sought to improve cell-(nano)particles' interactions through the mechanical modulation of the cell behavior in response to the delivery of non-viral vectors. The first part of this thesis was thus aimed at highlighting the importance of vector chemistry on the structure-function relationship of such kinds of materials, with a focus on lipid-based carriers. Furthermore, I dealt with the characterization of a novel class of lipid-based vectors to investigate the interconnection between their structure and ultimate gene transfer ability. This thesis next explored novel ways to improve the performances of polyethyleneimine (PEI), namely the gold standard polymer vector, both in linear (lPEI) and branched (bPEI) topography. First, a thorough investigation of all the experimental variables affecting the performances of PEI-based polyplexes was carried out to disclose the best working conditions of PEI-based carriers and improve the standardization of in vitro screening protocols. Next, I focused on the development of a vector-based approach to functionalize bPEI with targeting moieties to improve the vector's selectivity towards a specific cell type. We thus synthesized a series of bPEI conjugates incorporating targeting peptides to selectively deliver genes to vascular smooth muscle cells (vSMCs). Moreover, the targeting vectors were incorporated into a polyplex releasing matrix to enable their local and controlled release for cardiovascular-related approaches. Through the conjugation of an elastin-derived peptide sequence to the bPEI structure, we were able to improve the polymer's effectiveness on target vSMCs while leaving off-target cells unaffected, a fact that is especially relevant for the translation of non-viral gene delivery approaches in vivo. On the other side, a novel strategy based on the regulation of cell response to the delivery of nanoparticles was devised. Indeed, cells in vivo are constantly subjected to different environmental cues that govern some key cell functions. We thus investigated the application of an exogenous mechanical stimulus in terms of vibrational loading to cells undergoing transfection (i.e., the delivery of NAs utilizing non-viral vectors) using lPEI and bPEI-based polyplexes. Interestingly, mechanical stimuli applied to cells improved polyplex internalization by triggering the activation of clathrin-mediated endocytosis (CME), thus leading to greater transfection outcomes. This strategy outlined the importance of cell responses to exogenous cues on the ultimate internalization and expression of a gene of interest and set the stage for a novel way to deal with the non-viral delivery issue. Overall, the big picture drawn by this Ph.D. project highlighted the suitability of chemical-based approaches and cell-based approaches as promising ways to improve non-viral vector effectiveness. Further improvement in non-viral gene delivery research might be achieved by combining the strategies devised in this project. The development of multidisciplinary approaches taking into account both the delivery vector, the environment in which the delivery of genes takes place, and the cell response may thus pave the way to ever more effective strategies, and expedite the translation from the bench to the bedside of these materials.

Download or read book Gene Therapy and Gene Delivery Systems written by David V. Schaffer and published by Springer Science & Business Media. This book was released on 2005-12-20 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: 1 D.V. Schaffer, W. Zhou: Gene Therapy as Future Human Therapeutics.- 2 J. Heidel, S. Mishra, M.E. Davis: Molecular Conjugates.- 3 M. Manthorpe, P. Hobart, G. Hermanson, M. Ferrari, A. Geall, B. Goff, A. Rolland: Plasmid Vaccines and Therapeutics: From Design to Applications.- 4 S.R. Little, R. Langer: Non-Viral Delivery of Cancer Genetic Vaccines.- 5 J.C. Grieger, R.J. Samulski: Adeno-Associated Virus as a Gene Therapy Vector: Vector Development, Production and Clinical Applications.- 6 J.H. Yu, D.V. Schaffer: Advanced Targeting Strategies for Murine Retroviral and Adeno-Associated Viral Vectors.- 7 N. Loewen, E.M. Poeschla: Lentiviral Vectors.- 8 N.E. Altaras, J.G. Aunins, R.K. Evans, A. Kamen, J.O. Konz, J.J. Wolf: Production and Formulation of Adenovirus Vectors.-

Download or read book Nonviral Vectors for Gene Therapy written by and published by Academic Press. This book was released on 2014-11-18 with total page 437 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of genetics is rapidly evolving, and new medical breakthroughs are occurring as a result of advances in our knowledge of genetics. Advances in Genetics continually publishes important reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines. Includes methods for testing with ethical, legal, and social implications Critically analyzes future directions Written and edited by recognized leaders in the field

Download or read book Advanced Gene Delivery written by Alain Rolland and published by CRC Press. This book was released on 2003-09-02 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: A practical resource for everyone involved in the gene therapy field and in the design of effective gene delivery systems, this volume presents an overview and update of recent advances in the field of non-viral methods for the in vivo transfer of therapeutic genes to biological targets using conventional routes of administration. Methods to control the spatial and temporal modulation of gene function in vivo as well as the level, duration, specificity, and fidelity of gene expression are described. The rational design and the applications of a variety of non-viral gene delivery systems, such as cationic lipid-, polymer-, and (poly) peptide-based systems, are exemplified for the control of location of therapeutic genes administered by various routes. Current and potential clinical applications of gene-based medicines are presented for the prevention, correction or modulation of diseases. Examples of current applications of plasmid-based systems for genetic vaccination, treatment of genetic disorders such as cystic fibrosis, and treatment of acquired diseases such as cancer are also provided.

Download or read book Cationic Gelatin pluronic based Nanoparticles as Novel Non viral Delivery Systems for Gene Therapy written by Osama Madkhali and published by . This book was released on 2018 with total page 181 pages. Available in PDF, EPUB and Kindle. Book excerpt: A delivery system is essential to protect the DNA from degradation because of the extracellular and intracellular barriers. Two main types of delivery systems have been used to deliver genes into the body: viral and non-viral vectors. Although viral vectors are still superior over non-viral vectors, non-viral types are a better and safer alternative due to the safety concern of viral vectors. The low transfection efficiency of non-viral vectors remains a challenge due to the barriers that must be tackled. An effective non-viral vector must fulfill many conditions in order to be able to handle these barriers. The vector should be biocompatible, biodegradable, able to interact with DNA and cell membrane, able to successfully escape the endosome, and finally, capable of entering the nucleus to express the required protein. Cationic polymers are one of the most effective non-viral delivery systems. Cationic polymer/DNA (also called polyplexes) are able to interact with the DNA through electrostatic interaction, which results in DNA complexation and condensation. Gelatin is a natural polymer that can be easily modified by increasing the positive charge to effectively interact with the DNA and the cell membrane. In this project, gelatin nanoparticles were prepared using the two-step desolvation method, and were modified with cholamine as a cationic agent. Pluronic block copolymers were subsequently added to protect the cationic gelatin/DNA from degradation, and to increase the circulation time. The interactions of gelatin/Pluronic/DNA with the model membranes DPPC-CHOL and POPC-CHOL were studied using Langmuir's monolayer study, as well as Brewster's angle microscopy at the air/water interface. Transfection efficiency and cell viability were then evaluated at COS-7 cells. The results revealed that gelatin nanoparticles were successfully modified, at which point the positive charge increased from +11 to +32. Additionally, cationic gelatin (CG) was able to interact with and neutralize the negative charge of the DNA. CG/Pluronic/DNA complexes was characterized by size and zeta potential, showing a small particle size and a positive charge. The interaction of CG/Pluronic/DNA complex with the model membranes demonstrated a fluidization effect, especially with CG and Pluronics, whereas DNA showed an ineffective and negligible condensation effect. With respect to transfection efficiency, CG results were poor compared to positive control jetPEIʼ, with no improvement after adding Pluronics. Gemini surfactant (GS) was also used in the transfection experiments in hope that it might improve the transfection efficiency of cationic gelatin. However, CG/GS showed some aggregation, and the positive charge decreased by increasing the CG, which resulted in lower transfection efficiency. Cell viability of the cells containing cationic gelatin was very high (similar to non-treated cells), which was confirmed by the safety of the gelatin, even after modification. More investigational studies and optimizations are required to understand the low transfection efficiency of cationic gelatin. These studies will help design more effective delivery vectors, either with gelatin or with any other non-viral system.

Download or read book Self Assembling Complexes for Gene Delivery written by Alexander V. Kabanov and published by Wiley-Blackwell. This book was released on 1998-05-29 with total page 492 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent years have witnessed an explosion of activity in the field of gene therapy. Following advances in our understanding of the molecular basis of disease, hopes are high that the tremendous potential market for drugs employing antisense nucleotides and genes will one day be fulfilled. However, many obstacles remain, not least problems in the technology of gene delivery systems. Much of today's research focuses on non-viral approaches to gene delivery. Of particular importance are supramolecular complexes formed between DNA and various natural and synthetic polymers and lipids, otherwise known as 'self-assembling complexes for gene delivery'. In view of this fact, the editors of this volume have assembled an international team of contributors to present up-to-date reviews of the major chemical, biological and clinical aspects of such gene delivery vectors. Reflecting the diversity of research in this field, this book comprehensively covers: * the principles of self-assembly * natural mechanisms for gene delivery to cells * cationic lipids and liposomes * polyelectrolyte DNA complexes * systemic biodistribution of drug delivery systems * targeting of conjugates for gene delivery * new approaches to gene delivery * clinical evaluation Self-assembling Complexes for Gene Delivery is an essential reference for all professionals with an interest in gene and antisense therapy or novel drug delivery systems, including medicinal and pharmaceutical chemists, clinicians, human geneticists, molecular biologists and pharmacologists.

Download or read book Novel Gene Therapy Approaches written by Ming Wei and published by BoD – Books on Demand. This book was released on 2013-02-13 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gene therapy has the potential to be a tailor-made therapeutic with increased specificity and decreased side effects that can offer a "cure" for many disorders. The aim of this book is to provide up-to-date reviews of the rapidly growing field of gene therapy. Chapters cover a large range of topics including methods of gene delivery, and identification of targets with several papers on cancer gene therapy. If more people become aware of the true nature and potential of gene therapy, perhaps we can achieve the full benefit of such an innovative approach for the treatment of a range of diseases, including cancer.

Download or read book Polymeric Gene Delivery written by Mansoor M. Amiji and published by CRC Press. This book was released on 2004-09-29 with total page 707 pages. Available in PDF, EPUB and Kindle. Book excerpt: To treat disease or correct genetic disorders using gene therapy, the most suitable vehicle must be able to deliver genes to the appropriate tissues and cells in the body in a specific as well as safe and effective manner. While viruses are the most popular vehicles to date, their disadvantages include toxicity, limited size of genes they can carry

Download or read book Recent Advances in Novel Drug Carrier Systems written by Ali Demir Sezer and published by BoD – Books on Demand. This book was released on 2012-10-31 with total page 516 pages. Available in PDF, EPUB and Kindle. Book excerpt: This contribution book collects reviews and original articles from eminent experts working in the interdisciplinary arena of novel drug delivery systems and their uses. From their direct and recent experience, the readers can achieve a wide vision on the new and ongoing potentialities of different drug delivery systems. Since the advent of analytical techniques and capabilities to measure particle sizes in nanometer ranges, there has been tremendous interest in the use of nanoparticles for more efficient methods of drug delivery. On the other hand, this reference discusses advances in the design, optimization, and adaptation of gene delivery systems for the treatment of cancer, cardiovascular, pulmonary, genetic, and infectious diseases, and considers assessment and review procedures involved in the development of gene-based pharmaceuticals.

Download or read book Nonviral Vectors for Gene Therapy Part 2 written by Leaf Huang and published by Elsevier. This book was released on 2005-08-01 with total page 398 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of non-viral vector research has rapidly progressed since the publication of the first edition. This new edition is expanded to two separate volumes that contain in-depth discussions of different non-viral approaches, including cationic liposomes and polymers, naked DNA and various physical methods of delivery, as well as a comprehensive coverage of the molecular biological designs of the plasmid DNA for reduced toxicity, prolonged expression and tissue or disease specific genes. New developments such as the toxicity of the non-viral vectors and recent advances in nucleic acid therapeutics are fully covered in these volumes.

Download or read book Cationic Polymers Based Non Viral Gene Carriers written by Atul Pathak and published by LAP Lambert Academic Publishing. This book was released on 2011-02 with total page 156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nucleic acids-based next generation biopharmaceuticals (i.e., oligonucleotides, siRNA) are potential therapeutic agents have ability to cope with various incurable diseases. However, several biological barriers present a challenge for efficient gene delivery. Inception of nanotechnology now offer numerous non-viral vectors that have been fabricated and found capable of transmitting the biopharmaceuticals into the cell and even into specific subcellular compartments like mitochondria. This book illustrates novel chemically modified polyallylamine and polyethylenimine based nano- vectors for enhanced gene delivery. Modification of these polymers using imidazolyl and polysaccharides such as hyaluronic acid, chondroitin sulfate and heparin not only improve cytotoxicity index but also provides site-specificity for cell-type specific gene delivery. Incorporation of targeting moiety minimizes the chance of potential adverse effects and also reduces the amount the amount of dose required to achieve desired therapeutic effects. Recent developments in formulation of efficient drug carriers showed potential to develop gene therapy again diseases like cancer.

Download or read book Polymeric Gene Delivery Systems written by Yiyun Cheng and published by Springer. This book was released on 2018-09-04 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: ​The series Topics in Current Chemistry Collections presents critical reviews from the journal Topics in Current Chemistry organized in topical volumes. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field. The chapter "Polymeric Nanoparticle-Mediated Gene Delivery for Lung Cancer Treatment" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Download or read book Bioinspired and Biomimetic Polymer Systems for Drug and Gene Delivery written by Zhongwei Gu and published by John Wiley & Sons. This book was released on 2014-12-04 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: Here, front-line researchers in the booming field of nanobiotechnology describe the most promising approaches for bioinspired drug delivery, encompassing small molecule delivery, delivery of therapeutic proteins and gene delivery. The carriers surveyed include polymeric, proteinaceous and lipid systems on the nanoscale, with a focus on their adaptability for different cargoes and target tissues. Thanks to the broad coverage of carriers as well as cargoes discussed, every researcher in the field will find valuable information here.

Download or read book Non viral Vectors for Gene Therapy written by Leaf Huang and published by Gulf Professional Publishing. This book was released on 2005 with total page 412 pages. Available in PDF, EPUB and Kindle. Book excerpt: Annotation The field of non-viral vector research has rapidly progressed since the publication of the first edition. This new edition is expanded to two separate volumes that contain in-depth discussions of different non-viral approaches, including cationic liposomes and polymers, naked DNA and various physical methods of delivery, as well as a comprehensive coverage of the molecular biological designs of the plasmid DNA for reduced toxicity, prolonged expression and tissue or disease specific genes. New developments such as the toxicity of the non-viral vectors and recent advances in nucleic acid therapeutics are fully covered in these volumes.