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Whats ´New In Gene Therapy Of Hemophilia.
CONCLUSION: Achieving a safe and efficient remedy for hemophilia A and B by means of GT vector engineering needs further improvement. No randomized or quasi-randomized clinical trials of GT for hemophilia have been found. Given it is in its incipient period, there is need for well-designed clinical trials to evaluate the long-term practicability, efficacy and risks of GT for PWH. PMID: 29446741 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - February 14, 2018 Category: Genetics & Stem Cells Authors: Rodriguez-Merchan EC Tags: Curr Gene Ther Source Type: research

Current Understanding Of Inflammatory Responses In Acute Kidney Injury.
Abstract Acute kidney injury has been a tough complex with increased mortality and morbidity. Inflammatory responses, including innate and adaptive immune responses, involve in the initiation and development of acute kidney injury, especially under the ischemic circumstances. Tubular cells and distinct immune cell subgroups play a critical role in the pathogenesis of inflammation. Current gene therapies show their benefits in renal repair. Here, we reviewed the renal inflammatory infiltration, inflammatory mediators, oxidative stress and potential signaling pathways, which give rise to the kidney diseases, in the ...
Source: Current Gene Therapy - February 13, 2018 Category: Genetics & Stem Cells Authors: Hu C, Sheng Y, Qian Z Tags: Curr Gene Ther Source Type: research

CX3CL1/CX3CR1 axis, as The Therapeutic Potential In Renal Diseases: Friend Or Foe?
Abstract The fractalkine receptor chemokine (C-X3-C motif) receptor 1 (CX3CR1) and its highly selective ligand CX3CL1 mediate chemotaxis and adhesion of immune cells, which are involved in the pathogenesis and progression of numerous inflammatory disorders and malignancies. The CX3CL1/CX3CR1 axis has recently drawn attention as a potential therapeutic target because it is involved in the ontogeny, homeostatic migration, or colonization of renal phagocytes. We performed a Medline/PubMed search to detect recently published studies that explored the relationship between the CX3CL1/CX3CR1 axis and renal diseases and d...
Source: Current Gene Therapy - February 13, 2018 Category: Genetics & Stem Cells Authors: Zhuang Q, Cheng K, Ming Y Tags: Curr Gene Ther Source Type: research

Epigenetic Regulation Of Regulatory T Cells In Kidney Disease And Transplantation.
Abstract Regulatory T (Treg) cells are a kind of immunosuppression cells, which have been used to treat autoimmune diseases and induce allograft tolerance in clinical trials. While Treg cells based therapy is a promising treatment for kidney diseases and an emerging concept for tolerance induction in renal transplantation, a better understanding of the functions and biology of Treg cells is needed to be able to optimally exploit them. Epigenetics regulation, which refers to potentially heritable alterations in gene expression without underlying changes of the nucleotide sequence, plays an important role in Treg ce...
Source: Current Gene Therapy - February 13, 2018 Category: Genetics & Stem Cells Authors: Liu Y, Peng B, Wu S, Xu N Tags: Curr Gene Ther Source Type: research

Gene Therapy In Kidney Transplantation: Evidence Of Efficacy And Future Directions.
Abstract Allograft loss remains a severe clinical problem after kidney transplantation. The molecular mechanism of graft loss is a complex process involving T and/or B cell activation, inflammation responses, autophagy and apoptosis. Since these pathways are involved in immune responses in kidney transplant rejection, application of genetic interference to inhibit specific pathways could present an effective targeted gene therapy method. Recent studies have successfully attempted to use gene therapy to target the key molecules involved in immune responses during transplantation. This strategy has the potential to ...
Source: Current Gene Therapy - February 13, 2018 Category: Genetics & Stem Cells Authors: Li J, Qi G, Tu G, Yang C, Rong R Tags: Curr Gene Ther Source Type: research

Gene-Modified Mesenchymal Stem Cell-Based Therapy In Renal Ischemia-Reperfusion Injury.
Abstract Acute kidney injury (AKI) is a common syndrome in the clinic and has become a worldwide public health problem. Renal ischemia-reperfusion injury (IRI) is the most common cause of AKI. So far, effective treatment is still lacking for renal IRI, resulting in a high mortality rate of AKI. Mesenchymal stem cells (MSCs), considered as a promising candidate for tissue repair and regenerative medicine have aroused an increasing concern in recent years for the capacity of self-renewal and multi-lineage differentiation. MSC-based therapy has drawn wide attention for its therapeutic potential in renal IRI. The admi...
Source: Current Gene Therapy - February 13, 2018 Category: Genetics & Stem Cells Authors: Xu H, Chen C, Hu L, Hou J Tags: Curr Gene Ther Source Type: research

How Do Dendritic Cells Play The Role In Ischemia/Reperfusion Triggered Kidney Allograft Rejection.
Abstract In deceased donors, ischemia/reperfusion injury (IRI) is an important cause of allograft dysfunction. Prolonged cold and warm ischemia time leads to a high risk of early post-transplant complications, including acute and chronic rejection. Ischemia not only up-regulates inflammatory cytokines and chemokines, but also enhances the expression of MHC-class II and adhesion molecules on epithelial and dendritic cells. Moreover, the danger associated molecular patterns (DAMPs) released from stressed or dying cells, not only cause or amplify tissue inflammation and trigger tissue repair in response to IRI, but a...
Source: Current Gene Therapy - February 13, 2018 Category: Genetics & Stem Cells Authors: Cai S, Ichimaru N, Takahara S Tags: Curr Gene Ther Source Type: research

Role of Complement Properdin in Renal Ischemia-Reperfusion Injury.
Abstract Renal ischemia-reperfusion injury (IRI) is one of the main causes of acute kidney injury (AKI), and may lead to chronic kidney disease. The high mortality rate of AKI has not changed in the last 5 decades due to non-recognition, nephrotoxin exposure, delayed diagnosis and lack of specific intervention. Complement activation plays important roles in IRI-induced AKI because of its association with immunity, inflammation, cell death and tissue repair. Nevertheless, the role of complement properdin, the sole positive regulator of the alternative pathway, in IRI-induced AKI has not been well defined. This revi...
Source: Current Gene Therapy - February 13, 2018 Category: Genetics & Stem Cells Authors: Zwaini Z, Dai H, Stover C, Yang B Tags: Curr Gene Ther Source Type: research

Role of Immune Cells in Diabetic Kidney Disease.
Abstract Diabetic kidney disease (DKD) is one of the major complications of diabetes mellitus (DM) and is currently the most common cause of end-stage renal disease (ESRD) worldwide. Traditionally, DKD is considered a disease which has nothing to do with the immune system, and the pathogenesis is mainly characterized to be metabolic disturbance. Recent growing evidence indicates immunologic and inflammatory mechanisms in the development and progression of DKD. This overview of macrophages, dendritic cells, T lymphocytes, B lymphocytes, neutrophils and mast cells is closely involved in the pathologic process of DKD...
Source: Current Gene Therapy - February 13, 2018 Category: Genetics & Stem Cells Authors: Yang X, Mou S Tags: Curr Gene Ther Source Type: research

Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis.
CONCLUSION: Our study suggests that adult stem cells derived exosomes could be a potential therapeutic agent to confer neuroprotection in neurodegenerative diseases like Alzheimer's disease. PMID: 29366415 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - January 24, 2018 Category: Genetics & Stem Cells Authors: Venugopal C, Shamir C, Senthilkumar S, Babu JV, Sonu PK, Nishtha KJ, Rai KS, Shobha K, Dhanushkodi A Tags: Curr Gene Ther Source Type: research

A New Era For Hemoglobinopathies: More Than One Curative Options.
Abstract Hemoglobinopathies, including severe β-thalassemia and sickle cell disease, represent the most common monogenic disorders worldwide. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only approved curative option for these syndromes, albeit limited to patients having a suitable donor. Gene therapy, by making use of the patient's own hematopoietic stem cells to introduce a normal copy of the β-globin gene by viral vectors, bridged the gap between the need for cure of patients with hemoglobinopathies and the lack of a donor, without incurring the immunological risks of allo-HSCT...
Source: Current Gene Therapy - January 19, 2018 Category: Genetics & Stem Cells Authors: Psatha N, Papayanni PG, Yannaki E Tags: Curr Gene Ther Source Type: research

Neurodegenerative Disorders Treatment: The MicroRNA Role.
Abstract Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and prion disease are not timely and effectively treated using conventional therapies. This emphasizes the need for alternative therapeutic approaches. In this respect, gene-based therapies have been adopted as potentially feasible alternative therapies, where the microRNA (miRNA) approach has experienced a great explosion in recent years. Because miRNAs have been shown to be implicated in the pathogenesis of several diseases including neurodegenerative diseases, they are intens...
Source: Current Gene Therapy - January 19, 2018 Category: Genetics & Stem Cells Authors: Ridolfi B, Abdel-Haq H Tags: Curr Gene Ther Source Type: research

Nonviral Delivery Systems For Cancer Gene Therapy: Strategies And Challenges.
Abstract Gene therapy has been receiving widespread attention due to its unique advantage in regulating the expression of specific target genes. In the field of cancer gene therapy, modulation of gene expression has been shown to decrease oncogenic factors in cancer cells or increase immune responses against cancer. Due to the macromolecular size and highly negative physicochemical features of plasmid DNA, efficient delivery systems are an essential ingredient for successful gene therapy. To date, a variety of nanostructures and materials have been studied as nonviral gene delivery systems. In this review, we will...
Source: Current Gene Therapy - January 19, 2018 Category: Genetics & Stem Cells Authors: Shim G, Kim D, Le QV, Park GT, Kwon T, Oh YK Tags: Curr Gene Ther Source Type: research

Molecular Adjuvants Based On Plasmids Encoding Protein Aggregation Domains Affect Bone Marrow Niche Homeostasis.
CONCLUSION: The above findings provide compelling support to the thesis that adjuvants based on plasmids encoding protein aggregation domains disrupt the physiological features of the bone marrow elements. PMID: 29303078 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - January 5, 2018 Category: Genetics & Stem Cells Authors: Sabbieti MG, Lacava G, Amaroli A, Marchetti L, Censi R, Di Martino P, Agas D Tags: Curr Gene Ther Source Type: research

The Progress of Gene Therapy for Leber`s Optic Hereditary Neuropathy.
Abstract Leber's Optic Hereditary Neuropathy (LHON) is a common cause of teenaged blindness in both eyes for which there is currently no effective treatment. In 1871, the German ophthalmologist Theodor Leber was the first to describe the clinical characteristics of his namesake disease, and through unremitting efforts over the past 100 years, researchers have continued to increase their understanding of LHON. In recent years, using gene therapy, several groups have obtained breakthroughs in the treatment of the disease. In this article, we will review the challenging journey that researchers faced towards our curr...
Source: Current Gene Therapy - November 29, 2017 Category: Genetics & Stem Cells Authors: Zhang Y, Tian Z, Yuan J, Liu C, Liu HL, Ma SQ, Li B Tags: Curr Gene Ther Source Type: research

CRISPR/Cas9 Editing to Facilitate and Expand Drug Discovery.
CONCLUSION: We review the literature and hurdles that have been overcome to develop the current generation of tools being used to enrich the drug discovery paradigm. PMID: 29173168 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - November 21, 2017 Category: Genetics & Stem Cells Authors: Robert F, Huang S, Pelletier J Tags: Curr Gene Ther Source Type: research

CRISPR/Cas9 Gene Editing: From Basic Mechanisms To Improved Strategies For Enhanced Genome Engineering In Vivo.
Abstract Targeted genome editing using the CRISPR/Cas9 technology is becoming a major area of research due to its high potential for the treatment of genetic diseases. Our understanding of this approach has expanded in recent years yet several new challenges have presented themselves as we explore the boundaries of this exciting new technology. Chief among these is improving the efficiency but also the preciseness of genome editing. The efficacy of CRISPR/Cas9 technology relies in part on the use of one of the major DNA repair pathways, Homologous recombination (HR), which is primarily active in S and G2 phases of...
Source: Current Gene Therapy - November 21, 2017 Category: Genetics & Stem Cells Authors: Salsman J, Masson JY, Orthwein A, Dellaire G Tags: Curr Gene Ther Source Type: research

First-In-Human Phase 1 CRISPR Gene Editing Cancer Trials: Are We Ready?
Abstract A prospective first-in-human Phase 1 CRISPR gene editing trial in the United States for patients with melanoma, synovial sarcoma, and multiple myeloma offers hope that gene editing tools may usefully treat human disease. An overarching ethical challenge with first-in-human Phase 1 clinical trials, however, is knowing when it is ethically acceptable to initiate such trials on the basis of safety and efficacy data obtained from pre-clinical studies. If the pre-clinical studies that inform trial design are themselves poorly designed - as a result of which the quality of pre-clinical evidence is deficient - t...
Source: Current Gene Therapy - November 21, 2017 Category: Genetics & Stem Cells Authors: Baylis F, McLeod M Tags: Curr Gene Ther Source Type: research

New Developments in CRISPR/Cas-based Functional Genomics and their Implications for Research using Zebrafish.
Abstract Genome editing using CRISPR/Cas9 has advanced very rapidly in its scope, versatility and ease of use. Zebrafish (Danio rerio) has been one of the vertebrate model species where CRISPR/Cas9 has been applied very extensively for many different purposes and with great success. In particular, disease modeling in zebrafish is useful for testing specific gene variants for pathogenicity in a preclinical setting. Here we describe multiple advances in diverse species and systems that can improve genome editing in zebrafish. To achieve temporal and spatial precision of genome editing, many new technologies can be a...
Source: Current Gene Therapy - November 21, 2017 Category: Genetics & Stem Cells Authors: Prykhozhij SV, Caceres L, Berman JN Tags: Curr Gene Ther Source Type: research

Therapeutic Applications of CRISPR/Cas for Duchenne Muscular Dystrophy.
CONCLUSIONS: Restoration of the wild type and shorter form of dystrophin highlights the therapeutic potential of CRISPR technology for DMD. PMID: 29173172 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - November 21, 2017 Category: Genetics & Stem Cells Authors: Wong TWY, Cohn RD Tags: Curr Gene Ther Source Type: research

Gene Therapy And Retinal Diseases.
Conclusion Gene therapy represents an emerging and promising therapeutic approach for the treatment not only of rare inherited retinal diseases but also much more common retinal pathologies. PMID: 29149824 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - November 16, 2017 Category: Genetics & Stem Cells Authors: Campa C, Gallenga CE, Bolletta E, Perri P Tags: Curr Gene Ther Source Type: research

Cardioprotective Effects Of Serca2a Overexpression Against Ischemia-Reperfusion-Induced Injuries In Rats.
CONCLUSION: Our findings demonstrated that the overexpression of Serca2a plays an important role in myocardial protection from I/R injury and postischemic functional recovery, which may be via anti-necrotic, anti-apoptotic and pro-autophagy signal pathways. Our research provides solid basic data and new perspective for clinical treatment in heart failure patients with long-term over-expression of Serca2a. PMID: 29141547 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - November 10, 2017 Category: Genetics & Stem Cells Authors: Jian Y, Tian LL, Wang LH, Zhao XD, Chen JW, Murao K, Zhu W, Dong L, Wang GQ, Sun WP, Zhang GX Tags: Curr Gene Ther Source Type: research

Challenges and Advances in Gene Therapy Approaches for Neurodegenerative Disorders.
CONCLUSION: This review highlights several key factors to be taken into consideration to design successful preclinical and clinical gene therapy experiments with respect to the vehicle of delivery and the route of administration to CNS-specific targets, with an additional focus on antisense oligonucleotide therapy and recent clinical trial developments. PMID: 29034834 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - October 13, 2017 Category: Genetics & Stem Cells Authors: Donde A, Wong PC, Chen LL Tags: Curr Gene Ther Source Type: research

Effect of Oral Nonionic Polymeric Micelles Delivered Parathyroid Hormone cDNA on Bone Density and Microarchitecture.
CONCLUSION: Results showed that bone mineral density, bone volume fraction, and trabecular thickness were significantly increased in Group 1 over time, compared with those in Group 2 and Group 3. In conclusion, significantly improved bone mineral density and bone microstructure were observed in ovariectomized rats treated with PTH (1-34) cDNA delivered by nonionic polymeric micelles. PMID: 28982328 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - October 4, 2017 Category: Genetics & Stem Cells Authors: Chen SH, Ko JY, Chou FF Tags: Curr Gene Ther Source Type: research

Comparative Study Of Adeno-Associated Virus, Adenovirus, Baculovirus And Lentivirus Vectors For Gene Therapy Of The Eyes.
Conclusion Our findings show that intravitreal gene delivery is safe and feasible with AAV, AdV and lentivirus vectors. PMID: 28982327 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - October 3, 2017 Category: Genetics & Stem Cells Authors: Kalesnykas G, Kokki E, Alasaarela L, Lesch HP, Tuulos T, Kinnunen K, Uusitalo H, Airenne K, Ylä-Herttuala S Tags: Curr Gene Ther Source Type: research

Editorial: Gene Therapy for Fanconi Anemia Enters a New Clinical Era.
PMID: 28929955 [PubMed - in process] (Source: Current Gene Therapy)
Source: Current Gene Therapy - September 22, 2017 Category: Genetics & Stem Cells Authors: Verhoeyen E Tags: Curr Gene Ther Source Type: research

MicroRNAs Mediated MMP Regulation: Current Diagnostic and Therapeutic Strategies for Metabolic Syndrome.
Abstract Metabolic syndrome (MS) is a global socioeconomic problem rapidly progressing in accordance with increasing body mass index (BMI) and age. It is a consortium of risk factors, such as dyslipidaemia, insulin resistance, leptin resistance, reduced adiponectin, glucose intolerance, hyperglycemia, and hypertension. Collectively, these factors accelerate the onset of type 2 diabetes mellitus, cardiovascular disease, stroke, and certain cancers such as breast, liver pancreatic, and colon cancer. Extracellular matrix (ECM) and basement membrane remodeling play a central role during pathogenesis of MS as they regu...
Source: Current Gene Therapy - July 7, 2017 Category: Genetics & Stem Cells Authors: Saxena S, Jain A, Rani V Tags: Curr Gene Ther Source Type: research

Non-viral Delivery Systems for breast cancer gene therapy.
CONCLUSION: In this review, we focus on recent advances in the intracellular delivery of DNA and siRNA to the cancer cells with emphasis on breast cancer. PMID: 28595562 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - June 6, 2017 Category: Genetics & Stem Cells Authors: Vaseghi G, Rafiee L, Javanmard SH Tags: Curr Gene Ther Source Type: research

Glioblastoma Targeted Gene Therapy based on pEGFP/p53-Loaded Superparamagnetic Iron Oxide Nanoparticles.
CONCLUSION: It could be concluded that a significant increase in total apoptosis was induced in cells by magnetic nanoparticles, coupled with exposure to a magnetic force (p ≤0.01) as compared with cells that were not exposed to magnetism. PMID: 28578643 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - June 4, 2017 Category: Genetics & Stem Cells Authors: Eslaminejad T, Nematollahi-Mahani SN, Ansari M Tags: Curr Gene Ther Source Type: research

Readthrough of SCN5A Nonsense Mutations R1623X and S1812X Question Gene-therapy in Brugada Syndrome.
CONCLUSIONS: These results demonstrated that readthrough-enhancing methods effectively suppressed nonsense mutations in SCN5A and restored the expression of full-length channels. But the restored channels may increase the risk of arrhythmia. The strategies for nonsense mutations suppression provides potential evidence for personalized medicine for the treatment of genetic disorders. PMID: 28552050 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - May 28, 2017 Category: Genetics & Stem Cells Authors: Teng S, Huang J, Gao Z, Hao J, Yang Y, Zhang S, Pu J, Hui R, Wu Y, Fan Z Tags: Curr Gene Ther Source Type: research

Editorial: Smart and Controllable Systems for Gene Delivery.
PMID: 28524008 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - May 17, 2017 Category: Genetics & Stem Cells Authors: Mostaghaci B Tags: Curr Gene Ther Source Type: research

Phage-Mediated Gene Therapy.
Abstract Bacteriophages (bacterial viruses) have long been under investigation as vectors for gene therapy. Similar to other viral vectors, the phage coat proteins have evolved over millions of years to protect the viral genome from degradation post injection, offering protection for the valuable therapeutic sequence. However, what sets phage apart from other viral gene delivery vectors is their safety for human use and the relative ease by which foreign molecules can be expressed on the phage outer surface, enabling highly targeted gene delivery. The latter property also makes phage a popular choice for gene ther...
Source: Current Gene Therapy - May 10, 2017 Category: Genetics & Stem Cells Authors: Hosseinidoust Z Tags: Curr Gene Ther Source Type: research

Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery.
This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical routes have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially...
Source: Current Gene Therapy - May 10, 2017 Category: Genetics & Stem Cells Authors: Amjadi M, Mostaghaci B, Sitti M Tags: Curr Gene Ther Source Type: research

Perspectives of Gene Therapies in Autosomal Dominant Polycystic Kidney Disease.
Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease in the clinic. The predominant clinical manifestation is bilateral and progressive cysts formation in the kidneys, impairs normal renal parenchyma, and ultimately leads to end-stage renal disease (ESRD). ADPKD is a heterogenic disease which is resulted from the mutations of PKD1 or PKD2 genes which encode polycystin-1 (PC1) and -2 (PC2), thereby multiple cell signaling pathways are involved. Although causative genes and aberrant signaling pathways have been investigated for decades, lack of effective and less ...
Source: Current Gene Therapy - May 10, 2017 Category: Genetics & Stem Cells Authors: Xu Y, Li A, Wu G, Liang C Tags: Curr Gene Ther Source Type: research

Smart micro/nano-robotic systems for gene delivery.
Abstract Small scale robotics have attracted growing attention for the prospect of targeting and accessing cell-sized sites, necessary for high precision biomedical applications and drug/gene delivery. The loss of controlled gene therapy, inducing systemic side effects and reduced therapeutic efficiency, can be settled utilizing these intelligent carriers. Newly proposed solutions for the main challenges of control, power supplying, gene release and final carrier extraction/degradation have shifted these smart miniature robots to the point of being employed for practical applications of transferring oligonucleotid...
Source: Current Gene Therapy - May 10, 2017 Category: Genetics & Stem Cells Authors: Pedram A, Pishkenari HN Tags: Curr Gene Ther Source Type: research

Lipid Nanoparticles as potential Gene Therapeutic Delivery Systems for oral Administration.
mmala I, Melero A Abstract Gene therapy has experimented an increasing attention in the last decades, due to its enormous potential applications in the medical field. It can be defined as the use of genes or genetic material (DNA, RNA, oligonucleotides) to treat or prevent a disease state, generally a genetic-based one. Other applications, like treating viral, bacterial or parasite infections or development of vaccines are gaining also interest. Efficient gene therapy is mainly dependent on the ability of the highly labile genetic material to reach the therapeutic target. For this purpose, different delivery syste...
Source: Current Gene Therapy - May 10, 2017 Category: Genetics & Stem Cells Authors: Dorraj G, José Carreras J, Núñez H, Abushammala I, Melero A Tags: Curr Gene Ther Source Type: research

Smart and controllable rAAV gene delivery carriers in progenitor cells for human musculoskeletal regenerative medicine with a focus on the articular cartilage.
Abstract Cell therapy using mesenchymal stem cells (MSCs) is a powerful tool for the treatment of various diseases and injuries. Still, important limitations including the large amounts of cells required for application in vivo and the age-related decline in lifespan, proliferation, and potency may hinder the use of MSCs in patients. In this regard, gene therapy may offer strong approaches to optimize the use of MSCs for regenerative medicine. Diverse nonviral and viral gene vehicles have been manipulated to genetically modify MSCs, among which the highly effective and relatively safe recombinant adeno-associated ...
Source: Current Gene Therapy - May 10, 2017 Category: Genetics & Stem Cells Authors: Rey-Rico A, Cucchiarini M Tags: Curr Gene Ther Source Type: research

Gene delivery particle engineering strategies for shape-dependent targeting of cells and tissues.
Abstract Successful gene delivery requires overcoming both systemic and intracellular obstacles before the nucleic acid cargo can successfully reach its tissue and subcellular target location. Non-viral mechanisms to enable targeting while avoiding off-target delivery have arisen via biological, chemical, and physical engineering strategies. Herein we will discuss the physical parameters in particle design that promote tissue- and cell-targeted delivery of genetic cargo. We will discuss systemic concerns, such as circulation, tissue localization, and clearance, as well as cell-scale obstacles, such as cellular upt...
Source: Current Gene Therapy - May 10, 2017 Category: Genetics & Stem Cells Authors: Kozielski KL, Sitti M Tags: Curr Gene Ther Source Type: research

Nucleic acids-based nanotherapeutics crossing the blood brain barrier.
Abstract The restless endeavors revealing the molecular pathways underlying many neurodegenerative diseases and brain tumors have paved the way for the introduction of the selective exogenous gene-based therapeutics. The implicated active biomolecules encompass mainly negatively-charged nucleic acids ranging from DNA, mRNA, non-coding RNAs (small-interfering RNA, siRNA, and microRNA, miRNA), to antisense oligonucleotides. They selectively interfere with the genes translational and/or transcriptional processes. Although many reviews previously addressed brain targeting, a thorough correlation between the molecular ...
Source: Current Gene Therapy - May 10, 2017 Category: Genetics & Stem Cells Authors: Nafee N, Gouda N Tags: Curr Gene Ther Source Type: research

Delivering siRNA with Dendrimers: In Vivo Applications.
o AP Abstract Over the last decades, gene therapy has emerged as a pioneering therapeutic approach to treat or prevent several diseases. Among the explored strategies, the short-term silencing of protein coding genes mediated by siRNAs has a good therapeutic potential in a clinical setting. However, the widespread use of siRNA will require the development of clinically suitable, safe and effective vehicles with the ability to complex and deliver siRNA into target cells with minimal toxicity. Lately, dendrimers have gained considerable attention as non-viral vectors in nucleic acid delivery due to their unique stru...
Source: Current Gene Therapy - May 10, 2017 Category: Genetics & Stem Cells Authors: Leiro V, Santos SD, Pêgo AP Tags: Curr Gene Ther Source Type: research

Potential gene therapy towards treating neurodegenerative diseases employing polymeric nanosystems.
Abstract Recent integrated approaches involving nanotechnology and gene therapy have accelerated development of efficient drug delivery to the central nervous system (CNS). Neurodegenerative disorders are closely associated with genetic inheritance and mutation. Nanotechnology has allowed effective engineering of various such polymeric structures. Moreover, availability of a wide array of polymeric materials has enabled fabrication of biocompatible and biodegradable delivery vehicles. Our review focuses on the ideal features and properties of polymeric nanoparticles that have enabled successful gene therapy for ne...
Source: Current Gene Therapy - May 10, 2017 Category: Genetics & Stem Cells Authors: Bangde P, Atale S, Dey A, Pandit A, Dandekar P, Jain R Tags: Curr Gene Ther Source Type: research

Mesenchymal stem cell-derived extracellular vesicles for renal repair.
Abstract Transplantation of autologous mesenchymal stem cells (MSCs) has been shown to attenuate renal injury and dysfunction in several animal models, and its efficacy is currently being tested in clinical trials for patients with renal disease. Accumulating evidence indicates that MSCs release extracellular vesicles (EVs) that deliver genes, microRNAs and proteins to recipient cells, acting as mediators of MSC paracrine actions. In this context, it is critical to characterize the MSC-derived EV cargo to elucidate their potential contribution to renal repair. In recent years, researchers have performed high-throu...
Source: Current Gene Therapy - April 12, 2017 Category: Genetics & Stem Cells Authors: Nargesi AA, Lerman LO, Eirin A Tags: Curr Gene Ther Source Type: research

New Japanese Regulatory Frameworks for Clinical Research and Marketing Authorization of Gene Therapy and Cellular Therapy Products.
Abstract In Japan, the Pharmaceuticals and Medical Devices Law was passed in 2014. In this new law, regenerative medical products were defined, and a conditional and term-limited approval system only for regenerative medical products was instituted. Gene therapy and adoptive cellular therapy are categorized as regenerative medical products. This law is intended for registration trials for marketing authorization. The Act on the Safety of Regenerative Medicine was also implemented in 2014. This act is intended for clinical research and medical practice involving processed cells other than registration trials. Under...
Source: Current Gene Therapy - April 6, 2017 Category: Genetics & Stem Cells Authors: Nagai S, Ozawa K Tags: Curr Gene Ther Source Type: research

The Adeno-Associated Virus - A Safe and Effective Vehicle For Liver-Specific Gene Therapy of Inherited and Non-Inherited Diseases.
Abstract The first human adeno-associated virus (AAV) was originally discovered in 1960s as a contaminant of adenovirus stocks preparation and thus it had not been of medical interest. Throughout last three decades AAV has gained popularity to be used in gene therapy, mainly due to its replicative defectiveness and lack of pathogenicity in human. In addition, the ability to mediate a stable and long-term expression in both non-dividing and dividing cells with specific tissue tropism makes AAV as one of the most promising candidates for therapeutic gene transfer to treat many genetic as well as non-genetic disorder...
Source: Current Gene Therapy - March 13, 2017 Category: Genetics & Stem Cells Authors: Mak KY, Rajapaksha IG, Angus PW, Herath CB Tags: Curr Gene Ther Source Type: research

Approaches to optimize gene therapy for the treatment of hematologic malignancies: Overcoming the Obstacles.
Abstract Gene transfer and oncolytic viruses provide new therapeutic approaches for the treatment of hematologic malignancies. However, it is still too early to introduce gene delivery or oncolytic viruses into standard clinical protocol. It is very important to discuss the obstacles that gene transfer and oncolytic virotherapy face for the further clinical application for treatment of hematologic malignancies, and updating the advances made to overcome them. The major concerns in this review include the approaches of the development of immuno-stimulatory gene transfer mediated-vaccination for leukemia therapy, RN...
Source: Current Gene Therapy - February 14, 2017 Category: Genetics & Stem Cells Authors: Jiang Y, Xia B, Zhang Y, Xu W Tags: Curr Gene Ther Source Type: research

A Vector Based on the Chicken Hypersensitive Site 4 Insulator Element Replicates Episomally in Mammalian Cell.
In conclusion, apart from a few free vector forms, the cHS4-containing vector mainly replicates episomally in mammalian cells and out-performs comparable systems in terms of yielding both higher expression levels and stability levels. PMID: 28155604 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - February 1, 2017 Category: Genetics & Stem Cells Authors: Zhang X, Wang XY, Jia YL, Guo X, Wang YF, Wang TY Tags: Curr Gene Ther Source Type: research

Lessons Learned from Two Decades of Clinical Trial Experience in Gene Therapy for Fanconi Anemia.
Abstract Allogeneic hematopoietic stem cell transplant is the only curative treatment for patients with the non-malignant bone marrow failure syndrome called Fanconi anemia (FA). However, early and late complications associated with this approach underscore the need for alternative treatments. Gene therapy approaches aiming to correct the genetic defect in the patient's own hematopoietic stem cells remain the most promising strategy to overcome FA-associated bone marrow failure. Yet, despite more than two decades of clinical research, a therapeutic "success" has not yet been achieved. Here we review the ...
Source: Current Gene Therapy - January 18, 2017 Category: Genetics & Stem Cells Authors: Adair JE, Sevilla J, de Heredia CD, Becker PS, Kiem HP, Bueren J Tags: Curr Gene Ther Source Type: research

Induced Pluripotency and Gene Editing in Fanconi anemia.
Abstract Induced pluripotent stem cells (iPSCs) represent an invaluable tool in a chromosomal instability syndrome such as Fanconi anemia (FA), as they can allow study of the molecular defects underlying this disease. Many other applications, such as its use as a platform to test different methods or compounds, could also be of interest. But the greatest impact of iPSCs may be in bone marrow failure diseases, as iPSCs could represent an unlimited source of autologous cells to apply in advanced treatments such as gene therapy. At the same time, genome editing constitutes the next generation of technology to further...
Source: Current Gene Therapy - January 17, 2017 Category: Genetics & Stem Cells Authors: Navarro S, Giorgetti A, Raya A, Tolar J Tags: Curr Gene Ther Source Type: research

Anchored Lentiviral Vector Episomes For Stem Cell Gene Therapy In Fanconi Anemia.
Abstract Fanconi anemia (FA) is an autosomal recessive¬, multisystem DNA repair disorder with prominent defects in hematopoietic stem cell maintenance that result in their progressive attrition and failure in early school age. Allogeneic stem cell transplantation has proved curative for patients with suitable donors. This, along with the characteristic survival advantage of phenotypically normal over non-corrected FA stem cells underscores the compelling rationale for stem cell gene therapy in FA. While integrating lentiviral vectors (LV) have become the preferred platform for genetic correction in several hem...
Source: Current Gene Therapy - January 12, 2017 Category: Genetics & Stem Cells Authors: Verghese SC, Kurre P Tags: Curr Gene Ther Source Type: research

Gene Therapy in Fanconi anemia: a matter of time, safety and gene transfer tool efficiency.
vy C, Rio P Abstract Fanconi anemia (FA) is a rare genetic syndrome characterized by progressive marrow failure. Gene therapy by infusion of FA-corrected autologous hematopoietic stem cells (HSCs) may offer a potential cure since it is a monogenetic disease with mutations in the FANC genes, coding for DNA repair enzymes (See review[1]). However, the collection of hCD34 +-cells in FA patients implies particular challenges because of the reduced numbers of progenitor cells present in their bone marrow (BM)[2] or mobilized peripheral blood[3-5]. In addition, the FA genetic defect fragilizes the HSCs[6]. These particu...
Source: Current Gene Therapy - January 8, 2017 Category: Genetics & Stem Cells Authors: Els V, Rodríguez FJ, Cosset FL, Lévy C, Rio P Tags: Curr Gene Ther Source Type: research