EDITOR-IN-CHIEF: Current Gene Therapy
University of Florida
University of Florida
Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases.
Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.
Background: Several methods have been investigated to effectively and safely transmit genes that stimulate cells to release therapeutic factor VIII (FVIII) and factor IX (FIX) into the circulation of people with hemophilia (PWH).
Objective: To review the role of gene therapy (GT) in PWH.
Methods: A Cochrane Library and PubMed (MEDLINE) search related to the role of GT in hemophilia was analyzed.
Results: The most promising vectors for hemophilia GT are adeno-associated virus (AAV) and lentivirus. Several gene methods are available to lessen risks related to random vector integration and insertional mutagenesis, based on designer nucleases or CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated system). However, off-target issues need to be more meticulously and widely evaluated. Some clinical studies on hemophilia B based on AAV have obtained transitory or subtherapeutic levels of FIX expression. Another problem is possible transitory liver toxicity. Therefore, to reduce unintentional immune responses, transitory immunosuppression must be used, particularly when administering high-vector doses. Codon-optimized FVIII or FIX transgenes are able to promote clotting factor expression levels. The inclusion of a hyper-active gain-of-function R338L mutation in the FIX gene (FIX-R338L [FIX Padua]) makes the procedure more effective.
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.
Breast cancer continues to be a leading cause of mortality among women. While at an early stage, localized breast cancer is easily treated; however, advanced stages of disease continue to carry a high mortality rate. The discrepancy in treatment success highlights that current treatments are insufficient to treat advanced-stage breast cancer. As new and improved treatments have been sought, one therapeutic approach has gained considerable attention. Oncolytic viruses are uniquely capable of targeting cancer cells through intrinsic or engineered means. They come in many forms, mainly from four major virus groups as defined by the Baltimore classification system. These vectors can target and kill cancer cells, and even stimulate immunotherapeutic effects in patients. This review discusses not only individual oncolytic viruses pursued in the context of breast cancer treatment but also the emergence of combination therapies with current or new therapies, which has become a particularly promising strategy for treatment of breast cancer. Overall, oncolytic virotherapy is a promising strategy for increased treatment efficacy for advanced breast cancer and consequently provides a unique platform for personalized treatments in patients.
Introduction: Mesenchymal Stem Cell (MSC) therapy in recent years has gained significant attention. Though the functional outcomes following MSC therapy for neurodegenerative diseases are convincing, various mechanisms for the functional recovery are being debated. Nevertheless, recent studies convincingly demonstrated that recovery following MSC therapy could be reiterated with MSC secretome per se thereby shifting the dogma from cell therapy to cell “based” therapy. In addition to various functional proteins, stem cell secretome also includes extracellular membrane vesicles like exosomes. Exosomes which are of “Nano” size have attracted significant interest as they can pass through the bloodbrain barrier far easily than macro size cells or growth factors. Exosomes act as a cargo between cells to bring about significant alterations in target cells. As the importance of exosomes is getting unveil, it is imperial to carry out a comprehensive study to evaluate the neuroprotective potential of exosomes as compared to conventional co-culture or total condition medium treatments.
Objective: Thus, the present study is designed to compare the neuroprotective potential of MSC derived exosomes with MSC-condition medium or neuron–MSC-co-culture system against kainic acid induced excitotoxicity in in vitro condition. The study also aims at comparing the neuroprotective efficacy of exosomes/condition medium/co-culture of two MSC viz., neural crest derived human Dental Pulp Stem Cells (hDPSC) and human Bone-Marrow Mesenchymal Stem Cells (hBM-MSC) to identify the appropriate MSC source for treating neurodegenerative diseases.
Result: Our results demonstrated that neuroprotective efficacy of MSC-exosomes is as efficient as MSC-condition medium or neuron-MSC co-culture system and treating degenerating hippocampal neurons with all three MSC based approaches could up-regulate host’s endogenous growth factor expressions and prevent apoptosis by activating cell survival PI3K-B-cell lymphoma-2 (Bcl-2) pathway.
Conclusion: Thus, the current study highlights the possibilities of treating neurodegenerative diseases with “Nano” size exosomes as opposed to transplanting billions of stem cells which inherit several disadvantages.
Tay-Sachs disease, caused by impaired β-N-acetylhexosaminidase activity, was the first GM2 gangliosidosis to be studied and one of the most severe and earliest lysosomal diseases to be described. The condition, associated with the pathological build-up of GM2 ganglioside, has acquired almost iconic status and serves as a paradigm in the study of lysosomal storage diseases. Inherited as a classical autosomal recessive disorder, this global disease of the nervous system induces developmental arrest with regression of attained milestones; neurodegeneration progresses rapidly to cause premature death in young children. There is no effective treatment beyond palliative care, and while the genetic basis of GM2 gangliosidosis is well established, the molecular and cellular events, from diseasecausing mutations and glycosphingolipid storage to disease manifestations, remain to be fully delineated. Several therapeutic approaches have been attempted in patients, including enzymatic augmentation, bone marrow transplantation, enzyme enhancement, and substrate reduction therapy. Hitherto, none of these stratagems has materially altered the course of the disease. Authentic animal models of GM2 gangliodidosis have facilitated in-depth evaluation of innovative applications such as gene transfer, which in contrast to other interventions, shows great promise. This review outlines current knowledge pertaining the pathobiology as well as potential innovative treatments for the GM2 gangliosidoses.
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Drug Delivery Letters Volume 8, Issue 1
Current Nanoscience Volume 14, Issue 2
Current Nanomedicine Volume 8, Issue 1
Current Gene Therapy Volume 17, Issue 5
Nanoscience & Nanotechnology-Asia Volume 8, Issue 1
Adolescent Psychiatry Volume 7, Issue 2
Journal: Current Gene Therapy
Introduction: 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-throughput sequencing and proteomic analysis to detect and identify genes, microRNAs, and proteins enriched in MSC-derived EVs.