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Author: Dominic W.. Malcolm Publisher: ISBN: Category : Languages : en Pages : 202
Book Description
"Small interfering RNA (siRNA) and microRNA (miRNA) are short double stranded RNA molecules that mediate posttranscriptional gene silencing via RNA interference by binding to or degrading complimentary target mRNA in the cytosol to inhibit translation. Though > 30 siRNA and miRNA candidates are in clinical trials for a variety of indications, none have yet to receive FDA-approval. Successful delivery is the critical barrier to therapeutic translation, and necessitates the need for multifunctional drug delivery systems (DDS). Barriers to delivery include nuclease-mediated degradation and phospholipid membrane impermeability. Furthermore, any DDS used must be cytocompatible and avoid off-target effects. The study herein provides a comprehensive characterization of a pH-responsive diblock copolymer nanoparticle (NP) siRNA DDS and its effects on mesenchymal stem cells (MSCs) for applications in regenerative medicine. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize a library of diblock copolymers to determine how polymer properties affect siRNA delivery. Results show this NP-siRNA delivery is effective in multiple therapeutic cell types in vitro, and that increasing NP core hydrophobicity provides greater cytocompatibility and gene silencing. This is achieved by increased pHresponsive membrane lytic activity allowing for better endosomal escape. Additionally, in vitro treatment conditions were identified that resulted in potent gene silencing with no acute cytotoxicity. However, NP-siRNA treatment resulted in a sustained reduction in hMSC metabolic activity, and RNAseq with enrichment analysis shows upregulation of anti-apoptotic gene expression and immune signaling pathways associated with siRNA immune stimulation. Colloidal stability is critical for effective NP DDS, and can be significantly altered in the presence of biological proteins. Therefore, an extensive characterization of this NP-siRNA DDS in the presence of serum reveals NP-siRNA aggregation, which significantly diminishes siRNA delivery in vitro. When delivered locally in vivo, cells take up NP-siRNA complexes in a non-aggregated state, emphasizing the importance of local delivery. Taken together this in-depth characterization of NP-mediated siRNA delivery establishes a solid foundation for the design of next generation NP-siRNA DDS for the delivery of siRNA/miRNA to MSCs."--Pages xiv-xv.
Author: Dominic W.. Malcolm Publisher: ISBN: Category : Languages : en Pages : 202
Book Description
"Small interfering RNA (siRNA) and microRNA (miRNA) are short double stranded RNA molecules that mediate posttranscriptional gene silencing via RNA interference by binding to or degrading complimentary target mRNA in the cytosol to inhibit translation. Though > 30 siRNA and miRNA candidates are in clinical trials for a variety of indications, none have yet to receive FDA-approval. Successful delivery is the critical barrier to therapeutic translation, and necessitates the need for multifunctional drug delivery systems (DDS). Barriers to delivery include nuclease-mediated degradation and phospholipid membrane impermeability. Furthermore, any DDS used must be cytocompatible and avoid off-target effects. The study herein provides a comprehensive characterization of a pH-responsive diblock copolymer nanoparticle (NP) siRNA DDS and its effects on mesenchymal stem cells (MSCs) for applications in regenerative medicine. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize a library of diblock copolymers to determine how polymer properties affect siRNA delivery. Results show this NP-siRNA delivery is effective in multiple therapeutic cell types in vitro, and that increasing NP core hydrophobicity provides greater cytocompatibility and gene silencing. This is achieved by increased pHresponsive membrane lytic activity allowing for better endosomal escape. Additionally, in vitro treatment conditions were identified that resulted in potent gene silencing with no acute cytotoxicity. However, NP-siRNA treatment resulted in a sustained reduction in hMSC metabolic activity, and RNAseq with enrichment analysis shows upregulation of anti-apoptotic gene expression and immune signaling pathways associated with siRNA immune stimulation. Colloidal stability is critical for effective NP DDS, and can be significantly altered in the presence of biological proteins. Therefore, an extensive characterization of this NP-siRNA DDS in the presence of serum reveals NP-siRNA aggregation, which significantly diminishes siRNA delivery in vitro. When delivered locally in vivo, cells take up NP-siRNA complexes in a non-aggregated state, emphasizing the importance of local delivery. Taken together this in-depth characterization of NP-mediated siRNA delivery establishes a solid foundation for the design of next generation NP-siRNA DDS for the delivery of siRNA/miRNA to MSCs."--Pages xiv-xv.
Author: Ulf Schmitz Publisher: Springer Science & Business Media ISBN: 9400755902 Category : Medical Languages : en Pages : 352
Book Description
This edited reflects the current state of knowledge about the role of microRNAs in the formation and progression of solid tumours. The main focus lies on computational methods and applications, together with cutting edge experimental techniques that are used to approach all aspects of microRNA regulation in cancer. We are sure that the emergence of high-throughput quantitative techniques will make this integrative approach absolutely necessary in the near future. This book will be a resource for researchers starting out with cancer microRNA research, but is also intended for the experienced researcher who wants to incorporate concepts and tools from systems biology and bioinformatics into his work. Bioinformaticians and modellers are provided with a general perspective on microRNA biology in cancer, and the state-of-the-art in computational microRNA biology.
Author: Yaoliang Tang Publisher: Academic Press ISBN: 0128004975 Category : Science Languages : en Pages : 287
Book Description
Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas – cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool. - Introduces the MSC-exosome mediated cell-cell communication - Covers the major functional benefits in current MSC-derived exosome studies - Discusses strategies for the use of MSC-derived exosomes in cardiovascular therapies
Author: Bin Wang Publisher: CRC Press ISBN: 9814411647 Category : Medical Languages : en Pages : 468
Book Description
In the past few decades there has been incredible growth in "bionano"-related research, which has been accompanied by numerous publications in this field. Although various compilations address topics related to deoxyribonucleic acid (DNA) and protein, there are few books that focus on determining the structure of ribonucleic acid (RNA) and using RNA as building blocks to construct nanoarchitectures for biomedical and healthcare applications. RNA Nanotechnology is a comprehensive volume that details both the traditional approaches and the latest developments in the field of RNA-related technology. This book targets a wide audience: a broad introduction provides a solid academic background for students, researchers, and scientists who are unfamiliar with the subject, while the in-depth descriptions and discussions are useful for advanced professionals. The book opens with reviews on the basic aspects of RNA biology, computational approaches for predicting RNA structures, and traditional and emerging experimental approaches for probing RNA structures. This section is followed by explorations of the latest research and discoveries in RNA nanotechnology, including the design and construction of RNA-based nanostructures. The final segment of the book includes descriptions and discussions of the potential biological and therapeutic applications of small RNA molecules, such as small/short interfering RNAs (siRNAs), microRNAs (miRNAs), RNA aptamers, and ribozymes.
Author: Cesar Lopez-Camarillo Publisher: CRC Press ISBN: 1466576774 Category : Medical Languages : en Pages : 426
Book Description
MicroRNA (miRNA) biology is a cutting-edge topic in basic as well as biomedical research. This is a specialized book focusing on the current understanding of the role of miRNAs in the development, progression, invasion, and metastasis of diverse types of cancer. It also reviews their potential for applications in cancer diagnosis, prognosis, and th
Author: Vinod Kumar Yata Publisher: Springer Nature ISBN: 3030471209 Category : Technology & Engineering Languages : en Pages : 340
Book Description
This book is the third volume on this subject and focuses on the recent advances of nanopharmaceuticals in cancer, dental, dermal and drug delivery applications and presents their safety, toxicity and therapeutic efficacy. The book also includes the transport phenomenon of nanomaterials and important pathways for drug delivery applications. It goes on to explain the toxicity of nanoparticles to different physiological systems and methods used to assess this for different organ systems using examples of in vivo systems.
Author: Ravin Narain Publisher: Woodhead Publishing ISBN: 0081005210 Category : Science Languages : en Pages : 303
Book Description
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
Author: Gaetano Lamberti Publisher: ISBN: 9783039362004 Category : Languages : en Pages : 286
Book Description
The new frontier of pharmaceutical sciences is gene therapy, which is the use of molecules able to interact directly with the expression of the genetic material of the patient as well as of the disease-causing guest (bacteria, virus, parasites, and tumor cells). Among the molecules of interest for gene therapy, a relevant role is played by small interfering RNA (siRNA) molecules able to interfere with the expression of genes of interest for some diseases. However, siRNA molecules, even if they are powerful as drugs, are difficult to deliver since they are sensitive to enzymes present in plasma and they are large and negatively charged, so are difficult to administer into the cell nuclei, since the cell walls are scarcely permeable to large molecules and are also negatively charged. Therefore, the focus of research on siRNA-based therapies is their delivery, which can be performed by chemical modification, association with aptamers or polycations, or embedding them into properly designed liposomes. This book is centered on the more recent development in siRNA delivery techniques toward the clinical applications of this potent class of drugs.
Author: Mahendra Rai Publisher: John Wiley & Sons ISBN: 1119769884 Category : Science Languages : en Pages : 448
Book Description
NANOTECHNOLOGY IN MEDICINE Discover thorough insights into the toxicology of nanomaterials used in medicine In Nanotechnology in Medicine: Toxicity and Safety, an expert team of nanotechnologists delivers a robust and up-to-date review of current and future applications of nanotechnology in medicine with a special focus on neurodegenerative diseases, cancer, diagnostics, nano-nutraceuticals, dermatology, and gene therapy. The editors offer resources that address nanomaterial safety, which tends to be the greatest hurdle to obtaining the benefits of nanomedicine in healthcare. The book is a one-stop resource for recent and comprehensive information on the toxico logical and safety aspects of nanotechnology used in human health and medicine. It provides readers with cutting-edge techniques for delivering therapeutic agents into targeted cellular compartments, cells, tissues, and organs by using nanoparticulate carriers. The book also offers methodological considerations for toxicity, safety, and risk assessment. Nanotechnology in Medicine: Toxicity and Safety also provides readers with: A thorough introduction to the nanotoxicological aspects of nanomedicine, including translational nanomedicine and nanomedicine personalization Comprehensive introductions to nanoparticle toxicity and safety, including selenium nanoparticles and metallic nanoparticles Practical discussions of nanotoxicology and drug delivery, including gene delivery using nanocarriers and the use of nanomaterials for ocular delivery applications In-depth examinations of nanotechnology ethics and the regulatory framework of nanotechnology and medicine Perfect for researchers, post-doctoral candidates, and specialists in the fields of nanotechnology, nanomaterials, and nanocarriers, Nanotechnology in Medicine: Toxicity and Safety will also prove to be an indispensable part of the libraries of nanoengineering, nanomedicine, and biopharmaceutical professionals and nanobiotechnologists.
Author: Dominic W.. Malcolm
Author: Dominic W.. Malcolm
Author: Ulf Schmitz
Author: Shijoy Mathew
Author: Yaoliang Tang
Author: Bin Wang
Author: Cesar Lopez-Camarillo
Author: Vinod Kumar Yata
Author: Ravin Narain
Author: Gaetano Lamberti
Author: Mahendra Rai