Current gene therapy最新文献

{"title":"The Role of RNA m⁶A Modification in Cancer Glycolytic Reprogramming.","authors":"Yuanqi Li,&nbsp;Hao Huang,&nbsp;Shaoxian Wu,&nbsp;You Zhou,&nbsp;Tao Huang,&nbsp;Jingting Jiang","doi":"10.2174/1566523222666220830150446","DOIUrl":"https://doi.org/10.2174/1566523222666220830150446","url":null,"abstract":"<p><p>As one of the main characteristics of neoplasia, metabolic reprogramming provides nutrition and energy to enhance cell proliferation and maintain environment homeostasis. Glycolysis is one of the most important components of cancer metabolism and the Warburg effect contributes to the competitive advantages of cancer cells in the threatened microenvironment. Studies show strong links between N⁶-methyladenosine (m⁶A) modification and metabolic recombination of cancer cells. As the most abundant modification in eukaryotic RNA, m⁶A methylation plays important roles in regulating RNA processing, including splicing, stability, transportation, translation and degradation. The aberration of m⁶A modification can be observed in a variety of diseases such as diabetes, neurological diseases and cancers. This review describes the mechanisms of m⁶A on cancer glycolysis and their applications in cancer therapy and prognosis evaluation, aiming to emphasize the importance of targeting m⁶A in modulating cancer metabolism.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 1","pages":"51-59"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9195094","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":"Lentiviral Micro-dystrophin Gene Treatment into Late-stage mdx Mice for Duchenne Muscular Dystrophy Disease.","authors":"Selen Abanuz Eren,&nbsp;Cihan Tastan,&nbsp;Kevser Buse Karadeniz,&nbsp;Raife Dilek Turan,&nbsp;Didem Cakirsoy,&nbsp;Derya Dilek Kancagi,&nbsp;Sevdican Ustun Yilmaz,&nbsp;Mustafa Oztatlici,&nbsp;Hulya Oztatlici,&nbsp;Samed Ozer,&nbsp;Gamze Tumentemur,&nbsp;Ahmet Tarık Baykal,&nbsp;Ercument Ovali","doi":"10.2174/1566523223666230407091317","DOIUrl":"https://doi.org/10.2174/1566523223666230407091317","url":null,"abstract":"<p><strong>Aim: </strong>Duchenne Muscular Dystrophy (DMD) results in a deficiency of dystrophin expression in patient muscle fibers, leading to progressive muscle degeneration. Treatment of DMD has undertaken current transformation with the advancement of novel gene therapy and molecular biology techniques, which are secure, well-tolerated, and effective therapeutic approaches.</p><p><strong>Introduction: </strong>DMD gene therapies have mainly focused on young DMD patients as in vivo animal model trials have been performed in 0-1-month DMD mice. However, it has not yet been answered how micro-dystrophin encoding lentiviral treatment affects Dystrophin expression and DMD symptoms in 10-month mdx mice.</p><p><strong>Methods: </strong>We planned to integrate the micro-Dystrophin gene sequence into the muscle cells by viral transfer, using micro-Dystrophin-encoding lentivirus to reduce the dystrophic pathology in late-stage dmd mice. The histopathological and physiological-functional regeneration activities of the lentiviralmicro- Dystrophin gene therapy methods were compared, along with changes in temporal Dystrophin expression and their functionality, toxicity, and gene expression level.</p><p><strong>Results: </strong>Here, we showed that the micro-dystrophin transgene transfers intramuscularly and intraperitoneally in late-stage dmd-mdx-4cv mice restored dystrophin expression in the skeletal and cardiac muscle (<i>p</i> <0.001). Furthermore, motor performance analysis, including hanging and tracking tests, improved statistically significantly after the treatment (<i>p</i> <0.05).</p><p><strong>Conclusion: </strong>Consequently, this study suggests that patients in the late stages of muscular dystrophy can benefit from lentiviral micro-dystrophin gene therapies to present an improvement in dystrophic muscle pathology.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 4","pages":"304-315"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9880916","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-based Genetic Therapy in Leukemia: Properties, Delivery, and Experimental Models.","authors":"Nayra Oliveira Prado,&nbsp;Denise Kusma Wosniaki,&nbsp;Anelis Maria Marin,&nbsp;Carolina Mathias,&nbsp;Heloisa Bruna Soligo Sanchuki,&nbsp;Dalila Luciola Zanette,&nbsp;Mateus Nóbrega Aoki","doi":"10.2174/1566523223666230426153622","DOIUrl":"https://doi.org/10.2174/1566523223666230426153622","url":null,"abstract":"<p><p>Leukemia is a type of cancer that affects white blood cells. In this disease, immature blood cells undergo genetic mutations, leading to excessive replication and reduced cell death compared to healthy cells. In cancer, there may be the activation of oncogenes and the deactivation of tumor suppressor genes that control certain cellular functions. Despite the undeniable contribution to the patient's recovery, conventional cancer treatments may have some not-so-beneficial effects. In this case, gene therapy appears as an alternative to classical treatments. Gene therapy delivers genetic material to cells to replace or modify dysfunctional genes, a safe method for neoplasms. One of the types of nucleic acids explored in gene therapy is microRNA (miRNA), a group of endogenous, non-proteincoding, small single-stranded RNA molecules involved in the regulation of gene expression, cell division, differentiation, angiogenesis, migration, apoptosis, and carcinogenesis. This review aims to bring together the most recent advances found in the literature on cancer gene therapy based on microRNAs in the oncological context, focusing on leukemia.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 4","pages":"245-260"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9883024","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":"A Complete Sojourn of Gene Therapy along with its Targeting Approaches for the Treatment of the Major Depressive Disorder.","authors":"Dilpreet Singh,&nbsp;G D Gupta","doi":"10.2174/1566523223666230601145632","DOIUrl":"https://doi.org/10.2174/1566523223666230601145632","url":null,"abstract":"<p><p>Approximately 2% to 3% of men and 6% to 7% of women suffer from severe depressive disorders. The existing drugs only partially relieve symptoms for roughly 40% of these patients. The majority of antidepressant drugs are based on theories that are now 50 to 60 years old, and the sector is in critical need of new drug development targets. In the recent decade, numerous genes have been connected to depression in animal models, and serious depression does run in families in humans, indicating both a genetic and environmental component. Depression has been linked to the malfunctioning of serotonin signaling genes, including <i>p11</i>, SERT, <i>etc</i>, according to earlier research. Gene therapy for depression has been found in some instances to be relatively safe, despite the fact that it may seem riskier and more invasive than medication. Hence, there is a growing field regarding the safest delivery mechanisms of these genes that treat major depressive disorders permanently. Hence, the present review summarized the delivery mechanisms of various genes responsible for depressive disorders along with their molecular mechanisms and delivery at the cellular level.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 4","pages":"276-290"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9883486","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 Dietary Phytochemicals in Targeting Human miRNAs for Cancer Prevention and Treatment.","authors":"Yasodha Kesavan,&nbsp;Shushrruth Sai Srinivasan,&nbsp;Surajit Pathak,&nbsp;Satish Ramalingam","doi":"10.2174/1566523223666230519124519","DOIUrl":"10.2174/1566523223666230519124519","url":null,"abstract":"<p><p>MicroRNAs (miRNAs - ~22 nucleotides) are a type of non-coding RNAs that are involved in post-transcriptional gene silencing. They are known to regulate gene expression in diverse biological processes, such as apoptosis, development, and differentiation. Several studies have demonstrated that cancer initiation and progression are highly regulated by miRNA expression. The nutrients present in the diet may regulate the different stages of carcinogenesis. Interestingly, plant-based foods, like fruits and vegetables, have been shown to play a significant role in cancer prevention. Phytochemicals are bioactive compounds derived from plant sources, and they have been shown to have antiinflammatory, antioxidant, and anticancer properties. Recent findings suggest that dietary phytochemicals, such as genistein, resveratrol, and curcumin, exert significant anticancer effects by regulating various miRNAs. In this review, we focus on the role of dietary phytochemicals in cancer prevention and treatment through the modulation of miRNA expression.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"343-355"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9890417","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":"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}