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Author: Di Chen
Publisher:
ISBN:
Category :
Languages : en
Pages : 388
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Book Description
RNAi has great potential in future therapeutics as it has the ability to regulating many disease-related genes. However, many barriers prevent practical applications. To overcome the barriers, the specific targeting, efficient delivery system, the validated gene and the potent siRNA sequence are all vital important. The studies throughout this thesis have been focued on examining the validation of three RNAi therapies for two different disease models: allergic contact dermatitis and melanoma. For allergic contact dermatitis, I developed and tested a novel topical delivery system for siRNAs targeting TNF? (siTNF?) and MyD88 siRNA (siMyD88). While siRNAs applied without the transdermal enhancer are ineffective, treatment with combined siMyD88 and siTNF? significantly attenuated contact hypersensitivity (CHS) symptoms in mice, and did so better than treatment with siMyD88 or siTNF? as single agents. This is the first demonstration of topical gene silencing of TNF? and MyD88 to treat allergic reactions, highlighting a potential clinical use of RNAi therapy for skin and allergic diseases. For melanoma, I examined two RNAi therapies using liposomes attached to mannose and folate ligand, respectively. We developed a novel DC (dendritic cell)-targeted siRNA delivery system using mannosed liposomes (Man-lipo) with encapsulated IDO siRNA (Man-lipo-siIDO), which preferentially knocks down IDO in DCs Mice treated with Man-lipo-siIDO had a delayed time of onset of implanted murine melanomas, increased survival time, reduced tumour size, and increased reactivity of T cells from spleen and lymph nodes against melanoma antigens. This study supports the concept that Man-lipo-siIDO has potential for development as an immune-targeting therapeutic anticancer agent. We constructed a liposomal folate receptor-targeting siRNA delivery system. Compared to controls (non-treatment mice, mice treated with Folate-lipo-siScramble, or with non-folate-lipo-siBRAF), mice treated with Folate-lipo-siBRAF had reduced tumour volume, lower tumour weight, and reduced expression of PCNA and vascular networks in tumour tissue. This study highlights the potential of Folate-lipo-siBRAF for development as an anticancer therapeutic agent. In conclusion, the therapies for allergic dermatitis that use topical delivery of siTNF? and siMyD88, for melanoma using the Man-lipo-siIDO or the Folate-lipo-siBRAF, have the potential to be effective RNAi therapies to treat allergic dermatitis and melanoma.
Author: Di Chen
Publisher:
ISBN:
Category :
Languages : en
Pages : 388
Get Book Here
Book Description
RNAi has great potential in future therapeutics as it has the ability to regulating many disease-related genes. However, many barriers prevent practical applications. To overcome the barriers, the specific targeting, efficient delivery system, the validated gene and the potent siRNA sequence are all vital important. The studies throughout this thesis have been focued on examining the validation of three RNAi therapies for two different disease models: allergic contact dermatitis and melanoma. For allergic contact dermatitis, I developed and tested a novel topical delivery system for siRNAs targeting TNF? (siTNF?) and MyD88 siRNA (siMyD88). While siRNAs applied without the transdermal enhancer are ineffective, treatment with combined siMyD88 and siTNF? significantly attenuated contact hypersensitivity (CHS) symptoms in mice, and did so better than treatment with siMyD88 or siTNF? as single agents. This is the first demonstration of topical gene silencing of TNF? and MyD88 to treat allergic reactions, highlighting a potential clinical use of RNAi therapy for skin and allergic diseases. For melanoma, I examined two RNAi therapies using liposomes attached to mannose and folate ligand, respectively. We developed a novel DC (dendritic cell)-targeted siRNA delivery system using mannosed liposomes (Man-lipo) with encapsulated IDO siRNA (Man-lipo-siIDO), which preferentially knocks down IDO in DCs Mice treated with Man-lipo-siIDO had a delayed time of onset of implanted murine melanomas, increased survival time, reduced tumour size, and increased reactivity of T cells from spleen and lymph nodes against melanoma antigens. This study supports the concept that Man-lipo-siIDO has potential for development as an immune-targeting therapeutic anticancer agent. We constructed a liposomal folate receptor-targeting siRNA delivery system. Compared to controls (non-treatment mice, mice treated with Folate-lipo-siScramble, or with non-folate-lipo-siBRAF), mice treated with Folate-lipo-siBRAF had reduced tumour volume, lower tumour weight, and reduced expression of PCNA and vascular networks in tumour tissue. This study highlights the potential of Folate-lipo-siBRAF for development as an anticancer therapeutic agent. In conclusion, the therapies for allergic dermatitis that use topical delivery of siTNF? and siMyD88, for melanoma using the Man-lipo-siIDO or the Folate-lipo-siBRAF, have the potential to be effective RNAi therapies to treat allergic dermatitis and melanoma.
Author: Kun Cheng
Publisher: John Wiley & Sons
ISBN: 1118610733
Category : Science
Languages : en
Pages : 660
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Book Description
Commonly used by researchers to develop technologies for modifying and studying genetic process, RNA interference (RNAi) has many potential uses in medicine, biotechnology, and functional genomics. This book covers all essential aspects involved in the development of RNAi therapeutics, providing detailed guidance on the challenges and opportunities of bringing RNAi technologies from bench to clinic. It explores the design and mechanism of RNAi molecules, delivery strategies, and therapeutic applications in various diseases. Preclinical, regulatory, market, and intellectual aspects of RNAi technologies are also covered.
Author: Gaetano Lamberti
Publisher:
ISBN: 9783039362004
Category :
Languages : en
Pages : 286
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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: Mouldy Sioud
Publisher: Humana Press
ISBN: 9781603275460
Category : Science
Languages : en
Pages : 472
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Book Description
RNA interference has become a key method in the suppression of gene expression and the development of therapeutic agents, yet there is still the problem of delivery, stability, and the danger of off-target effects such as the silencing of unwanted genes and activation of innate immunity. In siRNA and miRNA Gene Silencing: From Bench to Bedside, expert researchers explore the most recent advances in siRNA design, expression, delivery, in vivo imaging, and methods to minimize siRNA’s unwanted effects and promote successful use in patients. As part of the highly successful Methods in Molecular BiologyTM series, the chapters focus on their respective subjects with easy-to-use, up-to-date information, including several step-by-step laboratory protocols on topics such as new delivery formulations and strategies with promising applications in vitro and in vivo, validated therapeutic target genes, and components of miRNA function, biogenesis, and interference with virus infection. Comprehensive and cutting-edge, siRNA and miRNA Gene Silencing: From Bench to Bedside offers an excellent collection of chapters to aid all those with an interest in RNAi, gene regulation, and new therapies.
Author: Bin Wang
Publisher: CRC Press
ISBN: 9814411647
Category : Medical
Languages : en
Pages : 468
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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: R. K. Gaur
Publisher: CRC Press
ISBN: 1439873259
Category : Science
Languages : en
Pages : 380
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Book Description
RNAi technology is used for large-scale screens that systematically shut down each gene in the cell, which can help identify the components necessary for a particular cellular process or an event such as cell division. Exploitation of the pathway is also a promising tool in biotechnology and medicine. Introducing new technology in the study of RNA
Author: Kenneth A. Howard
Publisher: Springer Science & Business Media
ISBN: 1461447437
Category : Medical
Languages : en
Pages : 348
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Book Description
The enormous potential of siRNA as a therapeutic has led to an explosion of interest from the scientific community. There has been intense interest from Big Pharma to capitalise on this new technology but the fact remains that delivery is a key determinant in realizing the full clinical potential of RNA interference. There is an urgent need for better delivery methods to take this technology forward. This book addresses the role of different RNAi molecules in cellular processes as rational for diagnostic and therapeutic approaches. This book will cover RNAi therapeutic design to optimize siRNA potency and reduce off-target effects and current delivery technologies to overcome both intracellular and extracellular barriers. The reader will gain an insight into RNA interference from the cellular mechanisms to screening to siRNA design right through to diagnostic and therapeutic applications.
Author: John F. Reidhaar-Olson
Publisher: Humana Press
ISBN: 9781603272940
Category : Medical
Languages : en
Pages : 0
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Book Description
The phenomenon of RNA interference has rapidly moved from groundbreaking scientific discovery to promising therapeutic approach. However, even as RNAi-based drugs enter the clinic, significant challenges remain, particulary in the area of delivery. Therapeutic Applications of RNAi provides detailed protocols in key areas of current focus, including testing of delivery vehicles, identification of appropriate model systems, and evaluation of the effects of RNAi in vivo. Produced by a team of internationally renowned authors, the volume describes the therapeutic applications of RNAi and potential pitfalls in oncology, viral infections and CNS disease, using a variety of delivery methods, including liposomes, peptide-based nanoparticles, polycationic polymers, and viral vehicles. Written in the highly successful Methods in Molecular BiologyTM series format, the chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Therapeutic Applications of RNAi is an ideal guide for scientists attempting to solve the numerous challenges in this field and revolutionize the treatment of disease.
Author: Jens Kurreck
Publisher: Royal Society of Chemistry
ISBN: 0854041168
Category : Medical
Languages : en
Pages : 362
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Book Description
This book provides a compelling overall update on current status of RNA interference
Author: Volker A. Erdmann
Publisher: Springer Science & Business Media
ISBN: 3642121683
Category : Medical
Languages : en
Pages : 460
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Book Description
RNA technologies are the driving forces of modern medicine and biotechnology. They combine the fields of biochemistry, chemistry, molecular biology, cell biology, physics, nanotechnology and bioinformatics. The combination of these topics is set to revolutionize the medicine of tomorrow. After more than 15 years of extensive research in the field of RNA technologies, the first therapeutics are ready to reach the first patients. Thus we are witnessing the birth of a very exciting time in the development of molecular medicine, which will be based on the methods of RNA technologies. This volume is the first of a series. It covers various aspects of RNA interference and microRNAs, although antisense RNA applications, hammerhead ribozyme structure and function as well as non-coding RNAs are also discussed. The authors are internationally highly respected experts in the field of RNA technologies.
