Current gene therapy最新文献

{"title":"Anesthesia and Cancer: Something More than Avoiding Stress Response.","authors":"Aida Raigon Ponferrada,&nbsp;Salvador Romero Molina,&nbsp;Juan Carlos Molina Ruiz,&nbsp;Josefa Gomez Maldonado,&nbsp;Jose Luis Guerrero Orriach","doi":"10.2174/1566523223666230328165109","DOIUrl":"https://doi.org/10.2174/1566523223666230328165109","url":null,"abstract":"<p><p>Currently, an increasing prevalence has been reported in incidences of tumor pathologies. The influence of anesthetics drugs has been the subject of numerous studies. It has been reported that the use of certain drugs may have an impact on prognosis and survival. By investigating the action of these drugs on different metabolic pathways and their mechanisms of action, we can better understand how they influence various hallmarks of carcinogenesis and determine their potential impact on cancer progression. Some of the action pathways are widely known within oncology, being targets of specific treatments, such as PI3k/AKT/mTOR, EGFR, and Wnt/ β-catenin. This review performs a thorough dissection of the interaction between anesthetic drugs and oncological cell lines through cell signaling pathways and genetic, immune, and transcriptomic pathways. Through these underlying mechanisms, it aims to clarify the effect of the choice of anesthetic drug and its potential influence on the prognosis of oncological surgery.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 4","pages":"261-275"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10238921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPM8 as a Potential Biomarker and Therapeutic Target for Gastric Cancer Identified by a Combination of Text Mining and RNA Sequencing.","authors":"Na Kong,&nbsp;Wendong Li,&nbsp;Jun Zhang,&nbsp;Xin Wang,&nbsp;Lin Hu,&nbsp;Qiqi Xu","doi":"10.2174/1566523223666230529142423","DOIUrl":"https://doi.org/10.2174/1566523223666230529142423","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric cancer is a well-known malignant tumor that causes millions of deaths worldwide every year. Due to the lack of a specific biomarker for gastric cancer, most patients are diagnosed at an advanced stage of the disease which results in a poor prognosis and a higher death rate. Therefore, novel biomarkers are urgently needed for early diagnosis and to improve the survival rate.</p><p><strong>Methods: </strong>In this study, we conducted RNA sequencing of tumor samples from 21 patients with gastric cancer. A total of 3192 differentially expressed genes (1589 up-regulated and 1603 down-regulated) were identified. Subsequently, we applied a text-mining algorithm for further analysis of these data and selected 30 representative genes to investigate as candidates for novel biomarkers in gastric cancer.</p><p><strong>Results: </strong>Among these genes, we confirmed transient receptor potential melastatin 8 channels (TRPM8) as a novel biomarker based on Western blot and immunochemistry validation performed on 134 samples. Compared to normal gastric tissue, the tumor tissues exhibited a significantly higher expression level of TRPM8.</p><p><strong>Conclusion: </strong>This study provides insights into the underlying role of TRPM8 in cell proliferation. In addition, TRPM8 may be used as a potential therapeutic target for patients with gastric cancer.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 5","pages":"391-399"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miRNAs as Next-generation Therapy Vehicles in Breast Cancer.","authors":"Priyanka Thakur,&nbsp;Harshita Dahiya,&nbsp;Ankur Kaushal,&nbsp;Vijai Kumar Gupta,&nbsp;Adesh K Saini,&nbsp;Reena V Saini","doi":"10.2174/1566523223666230215103524","DOIUrl":"https://doi.org/10.2174/1566523223666230215103524","url":null,"abstract":"<p><p>The second most pervasive cancer affecting the survival of women across the world is breast cancer. One of the biggest challenges in breast cancer treatment is the chemoresistance of cancer cells to various medications after some time. Therefore, highly specific blood-based biomarkers are required for early breast cancer diagnosis to overcome chemoresistance and improve patient survival. These days, exosomal miRNAs have attracted much attention as early diagnostic blood-based biomarkers because of their high stability, secretion from malignant tumor cells, and excellent specificity for different breast cancer subtypes. In addition, exosomal miRNAs regulate cell proliferation, invasion, metastasis, and apoptosis by binding to the 3'UTR of their target genes and limiting their production. This review focuses on the functions of exosomal miRNAs in tumorigenesis via targeting multiple signaling pathways as well as chemosensitivity and resistance mechanisms. In addition, the growing pieces of evidence discussed in this review suggest that circulating exosomal miRNAs could be utilized as potential next-generation therapeutic target vehicles in the treatment of breast cancer.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 5","pages":"330-342"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDAlmc: A Novel Low-rank Matrix Completion Model for MiRNADisease Association Prediction by Integrating Similarities among MiRNAs and Diseases.","authors":"Kun Wang,&nbsp;Junlin Xu,&nbsp;Geng Tian,&nbsp;Yang Li,&nbsp;Xueying Zeng,&nbsp;Jialiang Yang","doi":"10.2174/1566523223666230419101405","DOIUrl":"https://doi.org/10.2174/1566523223666230419101405","url":null,"abstract":"<p><strong>Introduction: </strong>The importance of microRNAs (miRNAs) has been emphasized by an increasing number of studies, and it is well-known that miRNA dysregulation is associated with a variety of complex diseases. Revealing the associations between miRNAs and diseases are essential to disease prevention, diagnosis, and treatment.</p><p><strong>Methods: </strong>However, traditional experimental methods in validating the roles of miRNAs in diseases could be very expensive, labor-intensive and time-consuming. Thus, there is a growing interest in predicting miRNA-disease associations by computational methods. Though many computational methods are in this category, their prediction accuracy needs further improvement for downstream experimental validation. In this study, we proposed a novel model to predict miRNA-disease associations by low-rank matrix completion (MDAlmc) integrating miRNA functional similarity, disease semantic similarity, and known miRNA-disease associations. In the 5-fold cross-validation, MDAlmc achieved an average AUROC of 0.8709 and AUPRC of 0.4172, better than those of previous models.</p><p><strong>Results: </strong>Among the case studies of three important human diseases, the top 50 predicted miRNAs of 96% (breast tumors), 98% (lung tumors), and 90% (ovarian tumors) have been confirmed by previous literatures. And the unconfirmed miRNAs were also validated to be potential disease-associated miRNAs.</p><p><strong>Conclusion: </strong>MDAlmc is a valuable computational resource for miRNA-disease association prediction.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 4","pages":"316-327"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9883013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of BAY 2599023 in the Current Treatment Landscape of Hemophilia A Gene Therapy.","authors":"Steven W Pipe,&nbsp;Valder R Arruda,&nbsp;Claudia Lange,&nbsp;Stephen Kitchen,&nbsp;Hermann Eichler,&nbsp;Samuel Wadsworth","doi":"10.2174/1566523222666220914105729","DOIUrl":"https://doi.org/10.2174/1566523222666220914105729","url":null,"abstract":"<p><p>Hemophilia A, a single gene disorder leading to deficient Factor VIII (FVIII), is a suitable candidate for gene therapy. The aspiration is for single administration of a genetic therapy that would allow the production of endogenous FVIII sufficient to restore hemostasis and other biological processes. This would potentially result in reliable protection from bleeding and its associated physical and emotional impacts. Gene therapy offers the possibility of a clinically relevant improvement in disease phenotype and transformational improvement in quality of life, including an opportunity to engage in physical activities more confidently. Gene therapy products for hemophilia A in advanced clinical development use adeno-associated viral (AAV) vectors and a codon-optimized B-domain deleted FVIII transgene. However, the different AAV-based gene therapies have distinct design features, such as choice of vector capsid, enhancer and promoter regions, FVIII transgene sequence and manufacturing processes. These, in turn, impact patient eligibility, safety and efficacy. Ideally, gene therapy technology for hemophilia A should offer bleed protection, durable FVIII expression, broad eligibility and limited response variability between patients, and long-term safety. However, several limitations and challenges must be overcome. Here, we introduce the characteristics of the BAY 2599023 (AAVhu37.hFVIIIco, DTX 201) gene therapy product, including the low prevalence in the general population of anti-AAV-hu37 antibodies, as well as other gene therapy AAV products and approaches. We will examine how these can potentially meet the challenges of gene therapy, with the ultimate aim of improving the lives of patients with hemophilia A.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 2","pages":"81-95"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9483509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Therapy for Chronic Traumatic Brain Injury: Challenges in Resolving Long-term Consequences of Brain Damage.","authors":"Vipin V Dhote,&nbsp;Prem Samundre,&nbsp;Aman B Upaganlawar,&nbsp;Aditya Ganeshpurkar","doi":"10.2174/1566523221666211123101441","DOIUrl":"https://doi.org/10.2174/1566523221666211123101441","url":null,"abstract":"<p><p>The gene therapy is alluring not only for CNS disorders but also for other pathological conditions. Gene therapy employs the insertion of a healthy gene into the identified genome to replace or replenish genes responsible for pathological disorder or damage due to trauma. The last decade has seen a drastic change in the understanding of vital aspects of gene therapy. Despite the complexity of traumatic brain injury (TBI), the advent of gene therapy in various neurodegenerative disorders has reinforced the ongoing efforts of alleviating TBI-related outcomes with gene therapy. The review highlights the genes modulated in response to TBI and evaluates their impact on the severity and duration of the injury. We have reviewed strategies that pinpointed the most relevant gene targets to restrict debilitating events of brain trauma and utilize vector of choice to deliver the gene of interest at the appropriate site. We have made an attempt to summarize the long-term neurobehavioral consequences of TBI due to numerous pathometabolic perturbations associated with a plethora of genes. Herein, we shed light on the basic pathological mechanisms of brain injury, genetic polymorphism in individuals susceptible to severe outcomes, modulation of gene expression due to TBI, and identification of genes for their possible use in gene therapy. The review also provides insights on the use of vectors and challenges in translations of this gene therapy to clinical practices.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 1","pages":"3-19"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9493094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA Theranostics in Cancer.","authors":"Sujay Paul","doi":"10.2174/156652322305230808102847","DOIUrl":"https://doi.org/10.2174/156652322305230808102847","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 5","pages":"329"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41095298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Long Non-Coding RNA in Regulating ER Stress Response to the Progression of Diabetic Complications.","authors":"Ramanarayanan Vijayalalitha,&nbsp;Architha Tca,&nbsp;George Raj Juanitaa,&nbsp;Ravichandran Jayasuriya,&nbsp;Karan Naresh Amin,&nbsp;Kunka Mohanram Ramkumar","doi":"10.2174/1566523222666220801141450","DOIUrl":"https://doi.org/10.2174/1566523222666220801141450","url":null,"abstract":"<p><p>Chronic hyperglycemia damages the nerves and blood vessels, culminating in other vascular complications. Such complications enhance cytokine, oxidative and endoplasmic reticulum (ER) stress. ER is the primary organelle where proteins are synthesised and attains confirmatory changes before its site of destination. Perturbation of ER homeostasis activates signaling sensors within its lumen, the unfolded protein response (UPR) that orchestrates ER stress and is extensively studied. Increased ER stress markers are reported in diabetic complications in addition to lncRNA that acts as an upstream marker inducing ER stress response. This review focuses on the mechanisms of lncRNA that regulate ER stress markers, especially during the progression of diabetic complications. Through this systemic review, we showcase the dysfunctional lncRNAs that act as a leading cause of ER stress response to the progression of diabetic complications.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 2","pages":"96-110"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9147906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mammalian Stable Cell Platforms for Recombinant Adeno-associated Virus (rAAV) Production: Development Strategies and their Impact on Viral Productivity.","authors":"Sofia Fernandes,&nbsp;Joana Diogo,&nbsp;Ana Sofia Coroadinha","doi":"10.2174/1566523223666230331111336","DOIUrl":"https://doi.org/10.2174/1566523223666230331111336","url":null,"abstract":"<p><p>Adeno-associated viruses (AAV) are widely used as a recombinant vectors in gene therapy. AAVs are non-pathogenic. They present reduced cytotoxicity and can transduce both dividing and non-dividing cells. The existence of different serotypes provides flexibility for targeting different tissues and organs. Its therapeutic success was already shown by the approval of three products by the European and American regulatory agencies. To satisfy the high dosage, safety, and reproducibility required in each clinical trial, production platforms based on stable mammalian cell lines have been proposed as the best strategy. However, the methodologies employed must be adapted to each cell line, which often results in distinct productivities. In this article, we review the published and commercially available mammalian stable cell lines, discussing the key factors that impact viral production yields, such as integration sites and copy numbers.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 3","pages":"184-197"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9809953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Throughput Sequencing Reveals N⁶-Methyladenosine-modified LncRNAs as Potential Biomarkers in Mice with Liver Fibrosis.","authors":"Furong Wu,&nbsp;Shengyu Zhang,&nbsp;Chang Fan,&nbsp;Shaopeng Huang,&nbsp;Hui Jiang,&nbsp;Jiafu Zhang","doi":"10.2174/1566523223666230606151013","DOIUrl":"10.2174/1566523223666230606151013","url":null,"abstract":"<p><strong>Background: </strong>N⁶-methyladenosine (m⁶A) is the most frequent internal modification in eukaryotic RNA. Long noncoding RNAs (lncRNAs) are a new type of noncoding regulatory molecule with multiple cellular functions. Both are closely related to the occurrence and development of liver fibrosis (LF). However, the role of m⁶A-methylated lncRNAs in the progression of LF remains largely unknown.</p><p><strong>Methods: </strong>In this study, HE and Masson staining were used to observe pathological changes in the liver, m⁶A-modified RNA immunoprecipitation sequencing (m⁶A-seq) was performed to systematically evaluate the m⁶A modification level of lncRNAs in LF mice, meRIP-qPCR and RT-qPCR were used to detect the m⁶A methylation level and RNA expression level of the target lncRNAs.</p><p><strong>Results: </strong>A total of 415 m⁶A peaks were detected in 313 lncRNAs in liver fibrosis tissues. There were 98 significantly different m⁶A peaks in LF, which were located on 84 lncRNAs, of which 45.2% of the lncRNA length was between 200-400 bp. At the same time, the first three chromosomes of these methylated lncRNAs were chromosomes 7, 5 and 1. RNA sequencing identified 154 differentially expressed lncRNAs in LF. The joint analysis of m⁶A-seq and RNA-seq found that there were three lncRNAs with significant changes in m⁶A methylation and RNA expression levels: lncRNA H19, lncRNA Gm16023 and lncRNA Gm17586. Subsequently, the verification results showed that the m⁶A methylation levels of lncRNA H19 and lncRNA Gm17586 were significantly increased, while that of lncRNA Gm16023 was significantly decreased, and the RNA expression of three lncRNAs was significantly decreased. Through the establishment of a lncRNA-miRNA-mRNA regulatory network, the possible regulatory relationships of lncRNA H19, lncRNA Gm16023 and lncRNA Gm17586 in LF were revealed.</p><p><strong>Conclusion: </strong>This study revealed the unique m⁶A methylation pattern of lncRNAs in LF mice, suggesting that the m⁶A methylation modification of lncRNAs is related to the occurrence and development of LF.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"371-390"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9577960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}