Current gene therapy最新文献

{"title":"Delivery of Superoxide Dismutase 3 Gene with Baculoviruses Inhibits TNF-α Triggers Vascular Smooth Muscle Cell Proliferation and Inflammation.","authors":"Shoa-Lin Lin, Song-Tay Lee, Shang-En Huang, Tsung-Hsien Chang, Yong-Jian Geng, Erna Sulistyowati, Jwu-Lai Yeh","doi":"10.2174/0115665232308789240823052607","DOIUrl":"https://doi.org/10.2174/0115665232308789240823052607","url":null,"abstract":"<p><strong>Background: </strong>Superoxide dismutase 3 (SOD3), recognized as a potent free radical scavenger, exhibits antioxidant, anti-inflammatory, and anti-angiogenic properties. However, the molecular mechanisms underlying the protective effects of SOD3 on the vascular smooth muscle cell during atherosclerosis remain unclear.</p><p><strong>Objectives: </strong>This study aimed to investigate the efficacy of the baculovirus expressing SOD3 gene delivery to vascular smooth muscle cells (VSMCs) and investigate whether the overexpression of SOD3 mitigates cell proliferation and migration induced by tumor necrosis factor-α (TNF-α).</p><p><strong>Methods: </strong>A baculoviral vector containing SOD3 cDNA (vAcMBac-CMV-IE-SOD3) was constructed and utilized to deliver the SOD3 gene into primary rat VSMCs. Cells were stimulated with recombinant TNF-α, and then cell proliferation and migration were evaluated using the bromodeoxyuridine and wound healing assay. Western blot was used to verify the expression of cell cycle regulators, cellular mediators, and proliferative biomarkers. Zymography, immunofluorescence staining, and ELISA assay were conducted to assess the expression levels of matrix metalloproteinases.</p><p><strong>Results: </strong>The results demonstrated efficient and non-cytotoxic transduction of vAcMBac- CMV-IE-SOD3 in VSMCs. SOD3 overexpression significantly suppressed cell proliferation and motility by inhibiting cell cycle regulators in TNF-α-induced cells. TNF-α elevated protein levels of phospho-ERK and phospho-Akt were reduced markedly by SOD3-overexpressing. Additionally, SOD3 overexpression attenuated the elevation of MMP-2 and MMP-9, the pro-inflammatory and proliferative biomarkers. Overall, the SOD3 gene delivery exhibited potent anti-proliferation and anti-inflammation effects on TNF-α-induced VSMCs.</p><p><strong>Conclusion: </strong>An effective SOD3 gene delivery using a recombinant baculoviral vector has been successfully established and is useful for overexpression of the SOD gene family. This approach provides new therapeutic strategies in gene therapy against atherosclerosis.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139560","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":"Recent Advances in Therapeutics and Manufacturing Processes of Recombinant Adeno-Associated Virus for the Treatment of Lung Diseases.","authors":"Luis Sorroza-Martinez, Mia Pelletier, David Guay, Bruno Gaillet","doi":"10.2174/0115665232294935240826061311","DOIUrl":"https://doi.org/10.2174/0115665232294935240826061311","url":null,"abstract":"<p><p>Developing delivery vectors capable of transducing genetic material across the lung epithelia and mucus barrier is a major challenge and of great interest to enable gene therapies to treat pulmonary diseases. Recombinant Adeno-associated Viruses (rAAVs) have emerged as attractive candidates among viral and non-viral vectors due to their broad tissue tropism, ability to transduce dividing and quiescent cells, and their safety profile in current human applications. While rAAVs have demonstrated safety in earlier clinical trials for lung disease applications, there are still some limitations regarding rAAV-transgene delivery in pulmonary cells. Thus, further improvements in rAAV engineering are needed to enhance the effectiveness of rAAV-based therapies for lung diseases. Such therapies could benefit patients with chronic lung diseases, such as asthma, chronic obstructive pulmonary disease, pulmonary hypertension, and cystic fibrosis, among others, by regulating hereditary gene mutations or acquired gene deregulations causing these conditions. Alongside therapeutic development, advances in the rAAV production process are essential to meet increasing production demands, while reducing manufacturing costs. This review discusses current challenges and recent advances in the field of rAAV engineering and manufacturing to encourage the clinical development of new pulmonary gene therapy treatments.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119189","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":"Hereditary Patterns and Genetic Associations in Obsessive-Compulsive Disorder (OCD): Neuropsychiatric Insights, Genetic Influences, and Treatment Perspectives.","authors":"Abhinay Dhiman, Sidharth Mehan, Zuber Khan, Aarti Tiwari, Ghanshyam Das Gupta, Acharan S Narula","doi":"10.2174/0115665232316708240828063527","DOIUrl":"https://doi.org/10.2174/0115665232316708240828063527","url":null,"abstract":"<p><p>Obsessive-Compulsive Disorder (OCD), a prevalent neuropsychiatric condition, affects approximately 2%-3% of the global population. This paper provides an extensive overview of OCD, detailing its clinical manifestations, neurobiological underpinnings, and therapeutic approaches. It examines OCD's classification shift in the DSM-5, the role of the cortico-striatothalamo- cortical pathway in its development, and the various factors contributing to its etiology, such as genes, environmental factors, and genetic predispositions. The challenges in diagnosing OCD and the effectiveness of both psychological and pharmacotherapeutic treatments are discussed. The paper also highlights the significant overlap between OCD and other mental health disorders, emphasizing its impact on global disability. Moreover, the role of genetic factors in OCD, including twin studies and gene association studies, is elaborated, underscoring the complex interplay of hereditary and environmental influences in its manifestation. The review further delves into the polygenic nature of OCD, illustrating how multiple genes contribute to its development, and explores the implications of genetic studies in understanding the disorder's complexity. Additionally, this research study delves into the concept of polygenic inheritance in complex diseases, highlighting the role of multiple genes in increasing OCD risk. A Genome-wide Association Study (GWAS) is employed to assess Single Nucleotide Polymorphisms (SNPs) to unearth genetic associations with OCD. This comprehensive analysis provides valuable insights into OCD's genetic landscape, paving the way for enhanced diagnostic approaches and treatment modalities.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105187","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":"miRNA-Targeted Vaccines: A Promising Approach for Viral Attenuation and Immunogenicity Enhancement.","authors":"Abhijit Debnath, Rupa Mazumder, Avijit Mazumder, Soumya Tripathi, Arpita Dua, Rajesh Singh, Saloni Mangal, Jahanvi Sanchitra, Pratibha Pandey, Biplab Pal, Hema Chaudhary, Parul Sharma, Shikha Srivastava","doi":"10.2174/0115665232305431240726113347","DOIUrl":"https://doi.org/10.2174/0115665232305431240726113347","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have emerged as a significant tool in the realm of vaccinology, offering novel approaches to vaccine development. This study investigates the potential of miRNAs in the development of advanced vaccines, with an emphasis on how they regulate immune response and control viral replication. We go over the molecular features of miRNAs, such as their capacity to direct post-transcriptional regulation toward mRNAs, hence regulating the expression of genes in diverse tissues and cells. This property is harnessed to develop live attenuated vaccines that are tissue-specific, enhancing safety and immunogenicity. The review highlights recent advancements in using miRNA-targeted vaccines against viruses like influenza, poliovirus, and tick-borne encephalitis virus, demonstrating their attenuated replication in specific tissues while retaining immunogenicity. We also explored the function of miRNAs in the biology of cancer, highlighting their potential to develop cancer vaccines through targeting miRNAs that are overexpressed in tumor cells. The difficulties in developing miRNA vaccines are also covered in this work, including delivery, stability, off-target effects, and the requirement for individualized cancer treatment plans. We wrap off by discussing the potential of miRNA vaccines and highlighting how they will influence the development of vaccination techniques for cancer and infectious diseases in the future.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874377","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":"Alternative Splicing of Pre-mRNA Matters in Oral Diseases.","authors":"Mingyang Yue, Rong Jia","doi":"10.2174/0115665232302948240718050212","DOIUrl":"https://doi.org/10.2174/0115665232302948240718050212","url":null,"abstract":"<p><p>Alternative splicing (AS) of pre-mRNA occurs widely in human genes to produce multiple isoforms with different or even opposite functions. Aberrant AS is often associated with gene mutations and can be corrected by gene therapy. Oral diseases are important public health problems worldwide. Accumulated pieces of evidence demonstrate that AS of pathogenic genes plays key roles in some oral diseases. However, considering the extensiveness and complexity of AS, it may affect the initiation and development of oral diseases deeply and widely. This review describes the diversity of AS and resulting isoforms in genetic, infectious, and malignant oral diseases and highlights the key roles of AS in determining the function of isoforms and the occurrence and progression of these diseases. The studies of alternative splicing may provide great opportunities for the understanding and treatment of oral diseases.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792136","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":"Knockdown of hsa_circ_0102231 Impedes the Progression of Liver Cancer through the miR-873-SOX4 Axis.","authors":"Jingyu Qian, Banghong Jiang, Zhongqiang Qin, Yulin Tan","doi":"10.2174/0115665232301878240627051455","DOIUrl":"https://doi.org/10.2174/0115665232301878240627051455","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity.</p><p><strong>Aim: </strong>The objective of this study was to investigate the role of circular RNA 0102231 (hsa_circ_ 0102231) in the progression of liver cancer.</p><p><strong>Methods: </strong>In this study, quantitative polymerase chain reaction experiments were performed to quantify the hsa_circ_0102231 level in different liver cancer cell lines. Bioinformatics analysis, as well as a dual-luciferase reporter and RNA pull-down assay, were used to identify putative hsa_circ_ 0102231 downstream targets. Colony formation and CCK8 assays were utilized to examine cell proliferation, whereas Transwell assays were employed to monitor cell migration. Lastly, the role of hsa_circ_0102231 in liver cancer was assessed in a subcutaneous xenograft model.</p><p><strong>Results: </strong>The expression of hsa_circ_0102231 increased significantly in HepG2 and Huh-7 cells compared with controls, and hsa_circ_0102231 knockdown inhibited cell proliferation and migration in vitro and in vivo. Bioinformatics analysis, as well as a dual-luciferase reporter and RNA pulldown assay, revealed that miR-873 and SOX4 were hsa_circ_0102231 downstream targets. miR-873 inhibition or SOX4 overexpression rescued the proliferation and migration of HepG2 and Huh-7 cells after hsa_circ_0102231 knockdown. Furthermore, SOX4 overexpression reversed the miR-873-induced inhibition of cell migration and proliferation in vitro.</p><p><strong>Conclusion: </strong>These results show that hsa_circ_0102231 knockdown impedes the progression of liver cancer by regulating the miR-873/SOX4 axis. However, further studies are needed to determine whether hsa_circ_0102231 may be a therapeutic target in liver cancer.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497366","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":"Significance of Ribonucleoside-diphosphate Reductase Subunit M2 in Lung Adenocarcinoma","authors":"Xiao-Jun Wang, Yun-Xia Huo, Peng-Jun Yang, Jing Gao, Weipeng Hu","doi":"10.2174/0115665232286359240611051307","DOIUrl":"https://doi.org/10.2174/0115665232286359240611051307","url":null,"abstract":"\u0000\u0000The Ribonucleoside-diphosphate Reductase subunit M2 (RRM2) is\u0000known to be overexpressed in various cancers, though its specific functional implications remain\u0000unclear. This aims to elucidate the role of RRM2 in the progression of Lung Adenocarcinoma (LUAD)\u0000by exploring its involvement and potential impact.\u0000\u0000\u0000\u0000RRM2 data were sourced from multiple databases to assess its diagnostic and prognostic\u0000significance in LUAD. We evaluated the association between RRM2 expression and immune\u0000cell infiltration, analyzed its function, and explored the effects of modulating RRM2 expression\u0000on LUAD cell characteristics through laboratory experiments.\u0000","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141351596","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":"Acetylresveratrol (AC-Res): An Evolving Frontier in Modulating Gene Expression.","authors":"Uttam Prasad Panigrahy, Rahul Subhash Buchade, Sandhya S, Anoop Kumar N, Sachinkumar Dnyaneshwar Gunjal, E Selvakumari, Narendra Kumar Pandey, Ankita Wal","doi":"10.2174/0115665232291487240603093218","DOIUrl":"https://doi.org/10.2174/0115665232291487240603093218","url":null,"abstract":"<p><strong>Background: </strong>Acetylresveratrol (AC-Res), to date, is a powerful stilbene phytoalexin generated organically or as a component of a plant's defensive system, is a significant plant phenolic chemical portion and is investigated as a therapy option for a number of disorders. Owing to its inadequate stabilisation and considerable conformation rigidity, the utility of AC-Res as a medication is limited.</p><p><strong>Objective: </strong>The current review article outlined the structure of AC-Res, their methods of activity, and the latest technological progress in the administration of these molecules. It is conceivable to deduce that AC-Res has a variety of consequences for the cellular functions of infected cells.</p><p><strong>Methods: </strong>The literature survey for the present article was gathered from the authentic data published by various peer-reviewed publishers employing Google Scholar and PubMedprioritizing Scopus and Web of Science indexed journals as the search platform focusing on AC-Res pharmacological actions, particularly in the English language.</p><p><strong>Result: </strong>Despite its extensive spectrum of biological and therapeutic applications, AC-Res has become a source of increasing concern. Depending on the researchers, AC-Res possesses radioprotective, cardioprotective, neurological, anti-inflammatory, and anti-microbial potential. It also has anti-cancer and antioxidant properties.</p><p><strong>Conclusion: </strong>To avoid non-specific cytotoxicity, optimization efforts are presently emphasizing the possible usage of AC-Res based on nanocrystals, nanoparticles and dendrimers, and nanocrystals. Finally, while using AC-Res in biology is still a way off, researchers agree that if they continue to explore it, AC-Res and similar parts will be recognized as actual possibilities for a variety of things in the next years.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300273","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":"The Role and Treatment Strategies of Ammonia-Related Metabolism in Tumor Microenvironment.","authors":"Qizhen Ye, Dan Li, Yi Zou, Ying Yuan","doi":"10.2174/0115665232301222240603100840","DOIUrl":"https://doi.org/10.2174/0115665232301222240603100840","url":null,"abstract":"<p><p>Tumor cells achieve their adaptability through various metabolic reprogramming processes. Among them, ammonia, as a traditional metabolic waste, plays an increasingly important role in the tumor microenvironment along with its associated metabolites. Other cells in the microenvironment can also reshape the immune status of the microenvironment by regulating ammonia-related metabolism, and targeting this metabolic aspect has emerged as a potential strategy for tumor treatment. In this study, we have systematically reviewed the source and destination of ammonia in tumor cells, as well as the links between ammonia and other biological processes. We have also analyzed the ammonia-related metabolic regulation of other cells (including T cells, macrophages, dendritic cells, natural killer cells, myeloid-derived suppressor cells, and stromal cells) in the tumor microenvironment, and summarized the tumor treatment methods that target this metabolism. Through ammonia-related metabolic reprogramming, tumor cells obtain the energy they need for rapid growth and proliferation. Multiple immune cells and stromal cells in the microenvironment also interact with each other through this metabolic regulation, ultimately leading to immune suppression. Despite the heterogeneity of tumors and the complexity of cellular functions, further research into therapeutic interventions targeting ammonia-related metabolism is warranted. This review has focused on the role and regulation of ammonia-related metabolism in tumor cells and other cells in the microenvironment, and highlighted the efficacy and prospects of targeted ammonia-related metabolism therapy.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300274","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":"Single-cell and Bulk Transcriptomic Analyses Reveal a Stemness and Circadian Rhythm Disturbance-related Signature Predicting Clinical Outcome and Immunotherapy Response in Hepatocellular Carcinoma.","authors":"Xiaojing Zhu, Zixin Zhang, Jiaxing Zhang, Yanqi Xiao, Hao Wang, Mingwei Wang, Minghui Jiang, Yan Xu","doi":"10.2174/0115665232298240240529131358","DOIUrl":"https://doi.org/10.2174/0115665232298240240529131358","url":null,"abstract":"<p><strong>Aims: </strong>Investigating the impact of stemness-related circadian rhythm disruption (SCRD) on hepatocellular carcinoma (HCC) prognosis and its potential as a predictor for immunotherapy response.</p><p><strong>Background: </strong>Circadian disruption has been linked to tumor progression through its effect on the stemness of cancer cells.</p><p><strong>Objective: </strong>Develop a novel signature for SCRD to accurately predict clinical outcomes and immune therapy response in patients with HCC.</p><p><strong>Methods: </strong>The stemness degree of patients with HCC was assessed based on the stemness index (mRNAsi). The co-expression circadian genes significantly correlated with mRNAsi were identified and defined as stemness- and circadian-related genes (SCRGs). The SCRD scores of samples and cells were calculated based on the SCRGs. Differentially expressed genes with a prognostic value between distinct SCRD groups were identified in bulk and single-cell datasets to develop an SCRD signature.</p><p><strong>Results: </strong>A higher SCRD score indicates a worse patient survival rate. Analysis of the tumor microenvironment revealed a significant correlation between SCRD and infiltrating immune cells. Heterogeneous expression patterns, functional states, genomic variants, and cell-cell interactions between two SCRD populations were revealed by transcriptomic, genomic, and interaction analyses. The robust SCRD signature for predicting immunotherapy response and prognosis in patients with HCC was developed and validated in multiple independent cohorts.</p><p><strong>Conclusions: </strong>In summary, distinct tumor immune microenvironment patterns were confirmed under SCRD in bulk and single-cell transcriptomic, and SCRD signature associated with clinical outcomes and immunotherapy response was developed and validated in HCC.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283271","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}