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Research progress on siRNA delivery with nonviral carriers
Gao Y, Liu XL, Li XR
International Journal of Nanomedicine , 2011, DOI: http://dx.doi.org/10.2147/IJN.S17040
Abstract: earch progress on siRNA delivery with nonviral carriers Review (9386) Total Article Views Authors: Gao Y, Liu XL, Li XR Published Date May 2011 Volume 2011:6 Pages 1017 - 1025 DOI: http://dx.doi.org/10.2147/IJN.S17040 Yan Gao*, Xin-Ling Liu*, Xiao-Rong Li Tianjin Medical University Eye Center, Tianjin, China *These two authors contributed equally to this work Abstract: RNA interference is a powerful method for the knockdown of pathologically relevant genes. Small interfering RNAs (siRNAs) have been widely demonstrated as effective biomedical genetic-therapy applications for many diseases. Unfortunately, siRNA duplexes are not ideal drug-like molecules. Problems hindering their effective application fundamentally lie in their delivery, stability, and off-target effects. Delivery systems provide solutions to many of the challenges facing siRNA therapeutics. Due to some fatal disadvantages of viral vectors, nonviral carriers have been studied extensively. Aside from liposomes, nanoparticles and cationic polymer carriers have exhibited improved in vivo stability, better biocompatibility, and efficiency for gene silencing with less cellular toxicity. They may represent a promising strategy for siRNA-based therapies, especially as nanomaterials. The present review also summarizes other methods of siRNA delivery and the side effects of the nanoparticles.
Recent Progress in Active Transdermal Drug Delivery Technologies  [cached]
Parul B. Patel,Mr. Amit Chaudhary,Dr. G. D. Gupta
Pharmaceutical Reviews , 2006,
Abstract: When one hears the words transdermal drug delivery, what comes to mind? More than likely one thinks about a simple patch that one stick onto skin like an adhesive bandage such as nicotine patch.Transdermal drug delivery system was first introduced more than 20 years ago. The technology generated tremendous excitement and interest amongst major pharmaceutical companies in the 1980s and 90s. By the mid to late 1990s, the trend of transdermal drug delivery system companies merging into larger organizations. Transdermal drug deliveries in the text of research articles grow continuously in the transdermal drug delivery 1980s, and has remained constant throughout the past decade.Innovations in technologies continue to occur at a positive rate, making the technology a fertile and vibrant are a of innovation, research and product development. In the present study, various new development in the field of TDDS are included to improve the release rate and other parameters on need base system and most suitable to the patient.Key Words:TDDS, active delivery, iontophoresis, electrophoresis, microneedle, needle-less injection, ultrasound, magnetophoresis, radio frequency, lasers.
Calcium Based Non-viral Gene Delivery: An Overview of Methodology and Applications
Kianoush Khosravi-Darani,Mohamaad Reza Mozafari,Ladan Rashidi,Mehrdad Mohammadi
Acta Medica Iranica , 2010,
Abstract: Application of therapeutic gene transfer in the treatment of genetic diseases is a notable progress but there are some disadvantages and limitations in it. The process of overcoming these barriers is a drastic change in gene delivery. Recently, calcium phosphate nanoparticles alone, or in combination with viral and nonviral vectors, were found to have a positive effect on gene transfer especially when incorporated in the colloidal particulate systems. This review elaborates on various successful methods of using calcium phosphate nanoparticles in gene delivery, which are considered an advancing approach to gene delivery.
Research progress on siRNA delivery with nonviral carriers  [cached]
Gao Y,Liu XL,Li XR
International Journal of Nanomedicine , 2011,
Abstract: Yan Gao*, Xin-Ling Liu*, Xiao-Rong LiTianjin Medical University Eye Center, Tianjin, China *These two authors contributed equally to this workAbstract: RNA interference is a powerful method for the knockdown of pathologically relevant genes. Small interfering RNAs (siRNAs) have been widely demonstrated as effective biomedical genetic-therapy applications for many diseases. Unfortunately, siRNA duplexes are not ideal drug-like molecules. Problems hindering their effective application fundamentally lie in their delivery, stability, and off-target effects. Delivery systems provide solutions to many of the challenges facing siRNA therapeutics. Due to some fatal disadvantages of viral vectors, nonviral carriers have been studied extensively. Aside from liposomes, nanoparticles and cationic polymer carriers have exhibited improved in vivo stability, better biocompatibility, and efficiency for gene silencing with less cellular toxicity. They may represent a promising strategy for siRNA-based therapies, especially as nanomaterials. The present review also summarizes other methods of siRNA delivery and the side effects of the nanoparticles.Keywords: small interfering RNA, nonviral vector, gene therapy, delivery system, nanoparticles, biocompatibility
"Bronchial Artery Delivery of Viral Vectors for Gene delivery in Cystic Fibrosis; Superior to Airway Delivery?"
Ameet Bakhai, Desmond J Sheridan, Charles C Coutelle
BMC Pulmonary Medicine , 2002, DOI: 10.1186/1471-2466-2-2
Abstract: We propose to inject gene delivery vectors directly into bronchial arteries combined with pre-delivery of vascular endothelial growth factor to increase vascular endothelial permeability and post-delivery flow reduction by balloon occlusion. Thus it may be possible to reach mucous secreting cells of the bronchial luminal epithelium and the submucosal glands in an increased and homogenous fashion.This combination of techniques to the best of our knowledge has not previously been investigated, and may enable us to overcome some of the current limitations to gene therapy for Cystic Fibrosis.Cystic fibrosis (CF) is the commonest, severe autosomal recessive disease in the UK, occurring in one child out of every 2500 new-borns. The disease is caused by mutations in the Cystic Fibrosis Transmenbrane Conductance Regulator (CFTR) gene, leading to production of defective CFTR protein, which disrupts chloride transport resulting in markedly impaired water fluxes across various epithelial layers. This leads to 'sticky' mucous secretions which obstruct the secretory glands of the lungs, digestive tract and other organs. In spite of considerable advances in the treatment of the intestinal symptoms, comparatively less progress has been achieved in the management of CF lung disease.To date, almost all attempts at gene therapy for the pulmonary manifestations of CF have relied on vector delivery via the airways. This work in animal models and human trials has demonstrated the ability to deliver genes by non-viral and viral gene transfer vectors to the airway epithelia by methods of inhalation, spray or bronchoscopic delivery. Although these investigations demonstrated that the general strategy of gene therapy for CF is hopeful, they also showed that the efficiency of even the presently most effective vector system, adenovirus, is still disappointingly low [2-9]. For adenovirus, this inefficiency is specifically due to the scarcity of the adenovirus fibre knob binding receptors: coxs
Novel Non-Viral Gene Carrier System: Recent Progress and Current Status  [cached]
Manju Rawat,,D. Singh,,Swarnlata Saraf,S. Saraf
Pharmaceutical Reviews , 2005,
Abstract: Safe, efficient and specific delivery of therapeutic genes remains an importantbottleneck for the development of gene therapy. The limitations of viral vectors,in particular their relative small capacity for therapeutic DNA, safety concerns,difficulty in targeting to specific cell types have led to evaluation and developmentof alternative vectors based on synthetic, non-viral systems. Synthetic, non-viralsystems have already been established and showed a unique pharmaceutical profilewith potential advantages for certain applications. The incorporation of new design criteria has led to recent advances towardfunctional delivery systems. This review focuses on the mechanistic aspectsof non-viral vectors such as cationic lipids, cationic polymers protein andpeptide, lipids, liposomes etc. delivery agents and novel method using vectorsystems. It can control gene expression especially for genes whose therapeuticeffects are considerably dependent on quantity, site, duration and timing eg.Temperature responsive vector system. The genesis of various agents is not herediscussed but this review discusses recent progress in various segments of syntheticpolymers that have recently been explored as delivery vehicles, focusing notonly on their strengths, but also on their limitations.
Rationally Designed Synthetic Vectors for Gene Delivery
Gururaj Rao, Preeti YadavaJeffrey Hughes
The Open Drug Delivery Journal , 2007, DOI: 10.2174/1874126600701010007]
Abstract: Vector development is one of the most important challenges facing the successful use of genes for treatment of diseases. Although chemically produced vectors offer distinct advantages over biological systems such as viruses, there are still some hurdles that have to be overcome before synthetic gene delivery vectors can be successfully implemented. This brief review discusses the biological barriers that limit current delivery strategies and reviews currently employed strategies for plasmid delivery. Nanoparticle-based gene delivery is reviewed along with methods for their characterization, physiochemical properties and toxicity. Finally a prospectus is provided for future development of an ideal synthetic gene delivery vector.
Perinatal systemic gene delivery using adeno-associated viral vectors  [PDF]
Rajvinder Karda,Giulia Massaro,Paul Gissen,Simon N. Waddington,Ahad A. Rahim
Frontiers in Molecular Neuroscience , 2014, DOI: 10.3389/fnmol.2014.00089
Abstract: Neurodegenerative monogenic diseases often affect tissues and organs beyond the nervous system. An effective treatment would require a systemic approach. The intravenous administration of novel therapies is ideal but is hampered by the inability of such drugs to cross the blood–brain barrier (BBB) and precludes efficacy in the central nervous system. A number of these early lethal intractable diseases also present devastating irreversible pathology at birth or soon after. Therefore, any therapy would ideally be administered during the perinatal period to prevent, stop, or ameliorate disease progression. The concept of perinatal gene therapy has moved a step further toward being a feasible approach to treating such disorders. This has primarily been driven by the recent discoveries that particular serotypes of adeno-associated virus (AAV) gene delivery vectors have the ability to cross the BBB following intravenous administration. Furthermore, safety has been demonstrated after perinatal administration mice and non-human primates. This review focuses on the progress made in using AAV to achieve systemic transduction and what this means for developing perinatal gene therapy for early lethal neurodegenerative diseases.
New Progress regarding the Use of Lactic Acid Bacteria as Live Delivery Vectors, Treatment of Diseases and Induction of Immune Responses in Different Host Species Focusing on Lactobacillus Species  [PDF]
Seria Masole Shonyela, Guan Wang, Wentao Yang, Guilian Yang, Chunfeng Wang
World Journal of Vaccines (WJV) , 2017, DOI: 10.4236/wjv.2017.74004
Abstract: Lactobacillus species are non-spore-forming, gram-positive bacteria and lactic acid producing bacteria (LAPB) that naturally inhabit the human and animal gastrointestinal and mouth organs. The aim of this review was to evaluate the new progress regarding the use of Lactobacillus species as live delivery vectors, prevention, and treatment of pathogenic and metabolic diseases. Lactobacillus strains of probiotics have been extensively studied and have confirmed that they can absolutely improve performance as live delivery vectors, a treatment option of various diseases such as: Hemorrhagic cecal coccidiosis in young poultry, hypertension, avian flu, obesity, diabetes, Derzsy’s disease or parvovirus infection, human immunodeficiency virus infections, irritable bowel syndrome, gastrointestinal disorders, Fungal infections, vaginal eubiosis, fish and shellfish species diseases. We give you an idea about that Lactobacillus species have been proficient in preventing and treating both disorders in animal models and some are used for clinical trials. We present the most current studies on the use of Lactobacillus strains that had an impact on an effective immune response to a specific antigen because a variety of antigens have been expressed. Therefore Lactobacillus strains can be considered as good candidates because of its potential for diseases treatment and vaccine development as heterologous protein secretion to date.
Tropism-Modification Strategies for Targeted Gene Delivery Using Adenoviral Vectors  [PDF]
Lynda Coughlan,Raul Alba,Alan L. Parker,Angela C. Bradshaw,Iain A. McNeish,Stuart A. Nicklin,Andrew H. Baker
Viruses , 2010, DOI: 10.3390/v2102290
Abstract: Achieving high efficiency, targeted gene delivery with adenoviral vectors is a long-standing goal in the field of clinical gene therapy. To achieve this, platform vectors must combine efficient retargeting strategies with detargeting modifications to ablate native receptor binding (i.e. CAR/integrins/heparan sulfate proteoglycans) and “bridging” interactions. “Bridging” interactions refer to coagulation factor binding, namely coagulation factor X (FX), which bridges hepatocyte transduction in vivo through engagement with surface expressed heparan sulfate proteoglycans (HSPGs). These interactions can contribute to the off-target sequestration of Ad5 in the liver and its characteristic dose-limiting hepatotoxicity, thereby significantly limiting the in vivo targeting efficiency and clinical potential of Ad5-based therapeutics. To date, various approaches to retargeting adenoviruses (Ad) have been described. These include genetic modification strategies to incorporate peptide ligands (within fiber knob domain, fiber shaft, penton base, pIX or hexon), pseudotyping of capsid proteins to include whole fiber substitutions or fiber knob chimeras, pseudotyping with non-human Ad species or with capsid proteins derived from other viral families, hexon hypervariable region (HVR) substitutions and adapter-based conjugation/crosslinking of scFv, growth factors or monoclonal antibodies directed against surface-expressed target antigens. In order to maximize retargeting, strategies which permit detargeting from undesirable interactions between the Ad capsid and components of the circulatory system (e.g. coagulation factors, erythrocytes, pre-existing neutralizing antibodies), can be employed simultaneously. Detargeting can be achieved by genetic ablation of native receptor-binding determinants, ablation of “bridging interactions” such as those which occur between the hexon of Ad5 and coagulation factor X (FX), or alternatively, through the use of polymer-coated “stealth” vectors which avoid these interactions. Simultaneous retargeting and detargeting can be achieved by combining multiple genetic and/or chemical modifications.
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