Current gene therapy最新文献

{"title":"Synergizing CRISPR-Cas9 with Advanced Artificial Intelligence and Machine Learning for Precision Drug Delivery: Technological Nexus and Regulatory Insights.","authors":"Amrita Arup Roy, Rahul Pokale, Anoushka Mukharya, Ajinkya N Nikam, Kamal Dua, Bola Sadashiva Satish Rao, Raviraja Neelavar Seetharam, Srinivas Mutalik","doi":"10.2174/0115665232342293241120033251","DOIUrl":"https://doi.org/10.2174/0115665232342293241120033251","url":null,"abstract":"<p><p>The evolution of genetic exploration tools, from laborious methods like radiationinduced mutations to the transformative CRISPR-Cas9 system, has fundamentally reshaped genetic research and gene editing capabilities. This journey, initiated by foundational techniques such as ZFNs and TALENs and culminating in the groundbreaking work of Doudna and Charpentier in 2012, has ushered in an era of precise DNA alteration and profound insights into gene functions. The CRISPR/Cas9 system uses the Cas9 enzyme and guides RNA (gRNA) to precisely target and cleave DNA, with subsequent repair via error-prone NHEJ or precise HDR, enabling versatile gene editing. Complementary computational tools like E-CRISP and Azimuth 2.0, alongside advanced deep learning models like DeepCRISPR, have significantly contributed to refining CRISPR experiments, optimizing gRNA efficiency, and predicting outcomes with greater precision. In clinical applications, CRISPR-Cas9 shows great promise for treating complex genetic disorders like sickle cell disease and β-thalassemia, but faces challenges such as off-target effects, immune responses to viral vectors, and ethical issues in germline editing. Overcoming these challenges requires meticulous experimentation and robust regulatory frameworks to ensure responsible and beneficial utilization of the CRISPR-Cas9 technology across diverse fields, including cancer treatment, genetic disease therapies, agriculture, and synthetic biology, while continually addressing ethical, safety, and legal considerations for its advancement and widespread adoption.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051893","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 of Immunotherapy in Lung Cancer Treatment: Current Strategies, Future Directions, and Insights into Metastasis and Immune Microenvironment.","authors":"Chen Lu Li, Xin Yuan Ma, Ping Yi","doi":"10.2174/0115665232340926241105064739","DOIUrl":"https://doi.org/10.2174/0115665232340926241105064739","url":null,"abstract":"<p><p>Lung cancer is a leading cause of mortality worldwide. Immunotherapy has emerged as a potentially effective strategy, as traditional medicines have shown minimal success. This review investigates the current state of immunotherapy for lung cancer treatment, focusing on its mechanisms, clinical applications, strategies, and future directions. This study focuses on the different characteristics of non-small and small-cell lung cancer to emphasize the need for targeted treatment strategies. In non-small cell lung cancer, immune checkpoint inhibitors that target PD-1, PDL1, and CTLA-4 have shown a strong therapeutic benefit and increased survival rates. The complex interactions among tumor cells, immune cells, and the tumor microenvironment significantly impact the outcome of immunotherapy. The determination of predicting biomarkers and conquering resistance requires an understanding of the tumor microenvironment. This study addresses a range of immunotherapeutic strategies, such as immune modulators, monoclonal antibodies, and cancer vaccines. The combination approaches are being explored to enhance treatment effectiveness and address resistance mechanisms that integrate immunotherapy with other modalities. Despite advancements, challenges still exist. The identification of reliable biomarkers, regulating immune- related adverse effects, and the overcoming of limitations in treating metastatic disease require more investigation. Future research directions should include exploring the immune microenvironment, developing personalized treatment strategies based on tumor profiles, and integrating new technologies for patient screening. Immunotherapy holds immense potential to modify lung cancer treatment and enhance clinical results.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946278","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":"Identification of the Metabolic Characteristic of Organ Fibrosis Using Microbial Analysis on RNA-seq Data.","authors":"Zitong Wang, Ping Wang, Guoyou He, Liang Cheng, Tianyu Li, Yan Wang, Hong Li","doi":"10.2174/0115665232257596231011110813","DOIUrl":"https://doi.org/10.2174/0115665232257596231011110813","url":null,"abstract":"<p><strong>Background: </strong>Fibrosis refers to abnormal deposition of extracellular matrix, which leads to organ dysfunction. Metabolic alterations, especially enhanced glycolysis and suppressed fatty acid oxidation, are recognized as an essential pathogenic process of fibrosis. Recently, several reports indicate that the changes in microbiota composition are associated with metabolic disorders, suggesting microbes may contribute to organ fibrosis by regulating metabolic processes.</p><p><strong>Method: </strong>In this study, microbial reannotation was carried out on the RNA-seq data of fibrotic organs. Then, the microbial composition differences among healthy and fibrotic organ samples were determined by alpha and beta diversity analysis. Common and specific microbial markers of fibrosis were also identified by LEfSe. After that, the correlation analysis of the characteristic microbe-- gene-functional pathway was conducted to confirm the effects of microbes on host metabolism.</p><p><strong>Result: </strong>The results showed that the microbial composition significantly differed between healthy and diseased organs. Besides, the common characteristic microbes interacted closely with each other and contributed to fibrosis through symbiosis or inhibition. The largest proportion in fibrosis organs was Proteobacteria, which was the main source of pathogenic microbes.</p><p><strong>Conclusion: </strong>Further study found that the metabolic alteration driven by common and special characteristic microbes in fibrotic organs focused on the processes related to glycolysis and fatty acid metabolism.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946276","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":"SLC2A3 is a Potential Factor for Head and Neck Squamous Cancer Development through Tumor Microenvironment Alteration.","authors":"Wei Jiang, Sheng Xu, Ping Li","doi":"10.2174/0115665232291300240509104344","DOIUrl":"10.2174/0115665232291300240509104344","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor immunity has garnered increasing attention in cancer treatment and progression. However, there is still a challenge in understanding the mechanisms of specific molecules affecting the clinical prognosis and tumor microenvironment (TME).</p><p><strong>Methods: </strong>Here, we applied the ESTIMATE algorithm to calculate the immune and stromal scores in 504 HNSC cases from TCGA. Patients were grouped according to the median value of the immune and stromal. Clinicopathological characteristics and differentially expressed genes (DEG) were analyzed. Subsequently, LASSO, COX regression, survival analysis, and clinicopathological characteristics were conducted. Subsequently, SLC2A3 was determined as a predictive factor that high expression of SLC2A3 at the mRNA and protein levels predicted a worse clinical prognosis. GSEA25099 was utilized for external validation of immune infiltration, while tissue PCR, IHC, and Western Blot were used to confirm the expression levels of SLC2A3.</p><p><strong>Results: </strong>A series of immune-infiltration analyses showed that SLC2A3 expression was negatively correlated with CD8+ T cells, significantly affecting the survival prognosis of HNSC. In the GSEA analysis, the high expression of SLC2A3 was mainly enriched for immune-related biological processes. Meanwhile, high expression of SLC2A3 possessed higher TIDE scores and was also strongly positively correlated with a series of immune checkpoints affecting survival prognosis, thus causing greater susceptibility to immune escape.</p><p><strong>Conclusion: </strong>Conclusively, SLC2A3 is a potential oncogene and factor of HNSC development, notably by an altered state of the immune microenvironment, immune-suppressive regulation, and immune escape.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"157-177"},"PeriodicalIF":3.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080504","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":"Neurotrophins as Potential Gene Therapy Targets for Huntington's Disease.","authors":"Sagor Kumar Roy, Ashima Barman, Kumary Labone Sarkar, Seidu A Richard, Bijal Arvinkumar Lacmane","doi":"10.2174/0115665232348486241025084202","DOIUrl":"https://doi.org/10.2174/0115665232348486241025084202","url":null,"abstract":"<p><p>\"Huntington's disease\" (HD) is an autosomal dominant hereditary neurodegenerative disease characterized by defects in efferent striatal neurons, cortical neurons, and the basal ganglia. The pathogenesis of HD is still unclear, and there is currently no curative therapy for this disorder. This review emphasizes the potential beneficial effects of various neurotrophic factors in HD. PubMed, Web of Science, Embase, and google scholar databases were used to search for all studies on the efficacy of neurotrophic factors in HD. Several gene therapy strategies have been employed to treat HD, including gene therapy with a variety of neuroprotective factors. Moreover, a wide variability of gene therapy approaches such as a neurotrophin, has shown promising results for both prevention and neuroprotection in HD, which may be due to their potential to prevent neuronal cell death or decrease neurodegeneration, thereby promoting the growth of innovative axons, dendrites, and synapses leading to improvement of HD. Neurotrophic factors may be suitable as neuroprotective therapy agents in HD. Therefore, substantial research on gene therapy should be conducted to provide better treatment options for HD in the future.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398545","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":"From DNA Editing to RNA Regulation: The Breakthroughs of CRISPR and Mega-CRISPR.","authors":"Dinesh Kumar, Debayan Sil, Komal, Balak Das Kurmi, Manish Kumar","doi":"10.2174/0115665232347515241128111207","DOIUrl":"https://doi.org/10.2174/0115665232347515241128111207","url":null,"abstract":"","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779615","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":"Unraveling Glioblastoma: TME Implication and Gene Therapy Advances.","authors":"Rohith Raali, Suresh P K","doi":"10.2174/0115665232351747241113050243","DOIUrl":"10.2174/0115665232351747241113050243","url":null,"abstract":"<p><p>Glioblastoma is a malignant manifestation of a solid brain tumour with a very dismal prognosis due to an overall median survival of 14 months. The currently administered Standard treatment plan, the STUPP regimen, is not very effective in tackling this neoplasia. A major concern that affects the development of new drug formulations, specifically for Glioma, is the inherent sub-clonal heterogeneity, which includes the dynamic and intricate nature of the Tumour Microenvironment (TME). Targeting the cellular niche using personalized medication for glioma specifically gene therapy, seems to be promising, with most studies in preclinical models yielding optimistic results. This paper analyses the great headways made in glioma gene therapy in the last 10 years while looking into different therapeutic strategies. That said, certain challenges do plague the clinical use of gene therapy which have been highlighted in the hopes that future researchers will address these concerns and further propel gene therapy in its journey from the Lab to the bedside.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616222","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":"Comprehensive Analysis and Experimental Validation of HEPACAM2 as a Potential Prognosis Biomarker and Immunotherapy Target in Colorectal Cancer.","authors":"Shouguang Wang, Lijuan Zhang, Dongbing Li, Miaomiao Gou","doi":"10.2174/0115665232325395241018103006","DOIUrl":"https://doi.org/10.2174/0115665232325395241018103006","url":null,"abstract":"<p><strong>Background: </strong>The role of HEPACAM family member 2 (HEPACAM2) is unclear in colorectal cancer (CRC).</p><p><strong>Objective: </strong>The objective of this study was to perform an extensive examination of HEPACAM2 and validate it experimentally in CRC.</p><p><strong>Methods: </strong>This study investigated the significance of HEPACAM2 in CRC and its potential diagnostic utility utilizing data from the Cancer Genome Atlas (TCGA) database. Additionally, the study examined potential regulatory networks involving HEPACAM2, including its associations with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), mRNA expression-based stemness index (mRNAsi), and drug sensitivity in CRC. The expression of HEPACAM2 was further validated using the GSE89076 dataset, and quantitative reverse transcription PCR (qRT-PCR) was employed to confirm HEPACAM2 expression levels in six pairs of CRC tissue samples.</p><p><strong>Results: </strong>HEPACAM2 exhibited abnormal expression patterns in various types of cancer, including CRC. A decrease in HEPACAM2 expression levels in CRC was found to be significantly correlated with the T stage (p < 0.001). Reduced HEPACAM2 expression in CRC patients was also linked to poorer overall survival (OS) (p = 0.007). The expression levels of HEPACAM2 in CRC patients were identified as an independent prognostic factor (p = 0.016). Furthermore, HEPACAM2 was associated with TCF-dependent signaling in response to WNT, G2/M checkpoints, and other pathways. The expression of HEPACAM2 in CRC was found to be associated with immune infiltration, immune checkpoint genes, TMB / MSI, and mRNAsi. Additionally, the expression of HEPACAM2 in CRC was significantly and inversely correlated with the drug sensitivities to gw772405x and 6-phenyl-6h-indeno[1,2-c]isoquinoline-5,11-dione. qRT-PCR confirmed that the expression level of HEPACAM2 was found to be lowly expressed in CRC tissues.</p><p><strong>Conclusion: </strong>These findings suggest that HEPACAM2 may serve as a potential prognostic biomarker and immunotherapeutic target for CRC patients.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567013","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":"Probing the Depths of Molecular Complexity: STAT3 as a Key Architect in Colorectal Cancer Pathogenesis.","authors":"Muhammad Suleman, Safir Ullah Khan, Shahid Ali, Abdullah Alghamdi, Mohammed Alissa, Rayan Y Mushtaq, Sergio Crovella","doi":"10.2174/0115665232336447241010094744","DOIUrl":"https://doi.org/10.2174/0115665232336447241010094744","url":null,"abstract":"<p><p>Colorectal cancer (CRC) has become a significant threat in recent decades, and its incidence is predicted to continue rising. Despite notable advancements in therapeutic strategies, managing CRC poses complex challenges, primarily due to the lack of clinically feasible therapeutic targets. Among the myriad molecules implicated in CRC, the signal transducer and activator of transcription 3 (STAT3) stands out as a promising target tightly regulated by various genes. This intracellular transcription factor, spanning 750-795 amino acids and weighing approximately 92 kDa, is crucial in key cellular activities such as growth, migration, invasion, inflammation, and angiogenesis. Aberrant activation of STAT3 signaling has been linked to various cancers, including CRC. Therefore, targeting this signaling pathway holds significance for potential CRC treatment strategies.STAT3, as a central intracellular transcription factor, is implicated in colorectal cancer development by activating aberrant signaling pathways. Numerous studies have demonstrated that the abnormal hyperactivation of STAT3 in CRC tissues enhances cell proliferation, suppresses apoptosis, promotes angiogenesis, and facilitates tumor invasion and metastasis. As a focal point in colorectal cancer research, STAT3 emerges as a promising candidate for detecting and treating CRC. This review aims to present recent data on STAT3, emphasizing the activation and functions of STAT3 inhibitors in CRC. Indeed, STAT3 inhibitors have been identified to have therapeutic potential in CRC, especially inhibitors targeting the DNA-binding domain (DBD). Indeed, STAT3 inhibitors have been identified to have a therapeutic potential in CRC, especially the inhibitors targeting the DNA binding domain (DBD). For example, imatinib acts by targeting cell surface receptors, and these inhibitors have shown potential for the control and treatment of tumor growth, angiogenesis, and metastasis. Imatinib, for example acts by targeting cell surface receptors, and these inhibitors have shown the future direction toward the control and treatment of tumor growth, angiogenesis, and metastasis.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544236","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":"Gene Augmentation Techniques to Stimulate Wound Healing Process: Progress and Prospects.","authors":"Jyotsana Dwivedi, Shubhi Kaushal, D Jeslin, L Karpagavalli, Rajesh Kumar, Dhruv Dev, Pranay Wal","doi":"10.2174/0115665232316799241008073042","DOIUrl":"https://doi.org/10.2174/0115665232316799241008073042","url":null,"abstract":"<p><p>Gene therapy has traditionally been used to treat individuals with late-stage cancers or congenital abnormalities. Numerous prospects for therapeutic genetic modifications have emerged with the discovery that gene therapy applications are far more extensive, particularly in skin and exterior wounds. Cutaneous wound healing is a complex, multistep process involving multiple steps and mediators that operate in a network of activation and inhibition processes. This setting presents a unique obstacle for gene delivery. Many gene delivery strategies have been developed, including liposomal administration, high-pressure injection, viral transfection, and the application of bare DNA. Among several gene transfer techniques, categorical polymers, nanoparticles, and liposomalbased constructs show great promise for non-viral gene transfer in wounds. Clinical experiments have shown that efficient transportation of certain polypeptides to the intended wound location is a crucial factor in wound healing. Genetically engineered cells can be used to produce and control the delivery of specific growth factors, thereby addressing the drawbacks of mechanically administered recombinant growth factors. We have discussed how repair mechanisms are based on molecules and cells, as well as their breakdown, and provided an overview of the methods and research conducted on gene transmission in tissue regeneration.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496572","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}