Current gene therapy最新文献

{"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}

{"title":"Immune Modulation Strategies in Gene Therapy: Overcoming Immune Barriers and Enhancing Efficacy.","authors":"Sivaprakasam S Amsaveni, Radha Mahendran, Vidhya C S, Dilip Kumar Chanchal, Sojomon Mathew, Mukesh Chandra Sharma, Jailani S, Syed Salman Ali","doi":"10.2174/0115665232305409240918040639","DOIUrl":"https://doi.org/10.2174/0115665232305409240918040639","url":null,"abstract":"<p><p>The immune system presents significant obstacles to gene therapy, which has limited its use in treating many illnesses. New approaches are needed to overcome these problems and improve the effectiveness of gene therapy. This study explores several techniques to immune regulation within gene therapy, a cutting-edge discipline that aims to optimise results by fine-tuning the immune response. We cover new ways to control the immune system and deliver therapeutic genes just where they are needed, including influencing immunological checkpoints, causing immunotolerance, and making smart use of immunomodulatory drugs. In addition, the study provides insight into new developments in the design of less immunogenic gene delivery vectors, which allow for the extension of transgene expression with minimal adverse immune reactions. In order to maximise the efficacy of gene-based therapies, this review analyses these novel approaches and gives a thorough overview of the present state of the art by addressing obstacles and pointing the way toward future developments in immune regulation. Not only does their integration provide new opportunities for the creation of safer and more effective gene treatments, but it also contains the key to overcome current obstacles.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364742","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 Gene Signatures Associated with COVID-19 across Children, Adolescents, and Adults in the Nasopharynx and Peripheral Blood by Using a Machine Learning Approach.","authors":"YuSheng Bao, JingXin Ren, Lei Chen, Wei Guo, KaiYan Feng, Tao Huang, Yu-Dong Cai","doi":"10.2174/0115665232316769240912061652","DOIUrl":"https://doi.org/10.2174/0115665232316769240912061652","url":null,"abstract":"<p><strong>Background: </strong>Significant variations in immune profiles across different age groups manifest distinct clinical symptoms and prognoses in Coronavirus Disease 2019 (COVID-19) patients. Predominantly, severe COVID-19 cases that require hospitalization occur in the elderly, with the risk of severe illness escalating with age among young adults, children, and adolescents.</p><p><strong>Objective: </strong>This study aimed to delineate the unique immune characteristics of COVID-19 across various age groups and evaluate the feasibility of detecting COVID-19-induced immune alterations through peripheral blood analysis.</p><p><strong>Methods: </strong>By employing a machine learning approach, we analyzed gene expression data from nasopharyngeal and peripheral blood samples of COVID-19 patients across different age brackets. Nasopharyngeal data reflected the immune response to COVID-19 in the upper respiratory tract, while peripheral blood samples provided insights into the overall immune system status. Both datasets encompassed COVID-19 patients and healthy controls, with patients divided into children, adolescents, and adult age groups. The analysis included the expression levels of 62,703 genes per patient. Then, 9 feature-sequencing methods (least absolute shrinkage and selection operator, light gradient boosting machine, Monte Carlo feature selection, random forest, ridge regression, adaptive boosting, categorical boosting, extremely randomized trees, and extreme gradient boosting) were employed to evaluate the association of the genes with COVID-19. Key genes were then utilized to develop efficient classification models.</p><p><strong>Results: </strong>The findings identified specific markers: insulin-like growth factor binding protein 3 (downregulated in the peripheral blood of COVID-19 patients), interferon alpha-inducible protein 27 (upregulated), and SERPING1 (upregulated in nasopharyngeal tissues). In addition, fibulin-2 was downregulated in adolescent patients, but upregulated in the other groups, while epoxide hydrolase 3 was upregulated in healthy controls, but downregulated in children and adolescents.</p><p><strong>Conclusion: </strong>This study offers valuable insights into the local and systemic immune responses of COVID-19 patients across age groups, aiding in identifying potential therapeutic targets and formulating personalized treatment strategies.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343126","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":"Pan-Cancer Single-Cell Analysis Revealing the Heterogeneity of Cancer-Associated Fibroblasts in Skin Tumors.","authors":"Yichi Zhang, Zhijie Zhao, Wenyi Huang, Byeong Seop Kim, Li Lin, Xin Li, Mengyuan Hou, Li Li, Yan Zhang, Wenjing Xi, Gang Chai","doi":"10.2174/0115665232331353240911080642","DOIUrl":"https://doi.org/10.2174/0115665232331353240911080642","url":null,"abstract":"<p><strong>Background: </strong>Cancer-Associated Fibroblasts (CAFs) constitute a heterogeneous group of cells critical for the remodeling of the tumor microenvironment (TME). Given their significant impact on tumor progression, particularly in skin cancers, a deeper understanding of their characteristics and functions is essential.</p><p><strong>Methods: </strong>This study employed a single-cell transcriptomic analysis to explore the diversity of CAFs within three major types of skin cancer: basal cell carcinoma, melanoma, and head and neck squamous cell carcinoma. We applied analytical techniques, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), pseudotime tracking, metabolic profiling, and stemness assessment to delineate and define the functional attributes of identified CAF subgroups.</p><p><strong>Results: </strong>Our analysis successfully delineated nine distinct CAF subgroups across the studied tumor types. Of particular interest, we identified a novel CAF subtype, designated as C0, exclusive to basal cell carcinoma. This subtype exhibits phenotypic traits associated with invasive and destructive capabilities, significantly correlating with the progression of basal cell carcinoma. The identification of this subgroup provides new insights into the role of CAFs in cancer biology and opens avenues for targeted therapeutic strategies.</p><p><strong>Conclusion: </strong>A pan-cancer analysis was performed on three cancers, BCC, MA, and HNSCC, focusing on tumor fibroblasts in TME. Unsupervised clustering categorized CAF into nine subpopulations, among which the C0 subpopulation had a strong correspondence with BCC-CAF and an invasive- destructive-related phenotype.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343127","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":"Target and Gene-Based Therapeutic Strategies against Pancreatic Cancer: Current and Future Prospects.","authors":"Medha Dwivedi, Sayak Sanyal, Sakshi Singh, Manish Dwivedi, Somali Sanyal","doi":"10.2174/0115665232320846240910055032","DOIUrl":"https://doi.org/10.2174/0115665232320846240910055032","url":null,"abstract":"<p><p>Despite tremendous advancements in knowledge, diagnosis, and availability of both traditional and innovative treatments, pancreatic cancer remains a dangerous disease with a high death rate and dismal prognosis. The traditional strategy in adjuvant and palliative settings is still cytotoxic chemotherapy predicated on the purine derivative gemcitabine; nevertheless, there is an increasing need for new medicines that target the primary molecular pathways and pathophysiological abnormalities implicated. There is now just a tiny amount of evidence of therapeutic benefit when the targeted drug erlotinib is added to the conventional gemcitabine treatment. In preclinical and clinical trials, novel medications targeting mTOR, NF-κB, and proteasome, including the enzyme histone deacetylase, are currently being studied alongside the well-established monoclonal antibody treatments and small-molecule protein tyrosine kinase inhibitors. These novel medications may change the negative natural progression of this illness in conjunction with gene therapy and immunotherapy, both of which are undergoing clinical study. In this regard, leveraging miRNA manipulation to combat cancer is appealing due to its promise to deliver personalized treatment tailored to an individual's distinct gene or miRNA expression profile. Preclinical studies involving animals have showcased the effectiveness of miRNA-based therapies, with several of these treatments now progressing into human clinical trials for various malignancies and other medical conditions. This review describes the important developments of targeted therapeutics that are associated with pancreatic cancer and the discoveries which can help in dealing with this fatal malignancy in a more significant manner.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343128","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 Oxidative Phosphorylation-Related Subtypes and Construction of a Prognostic Signature in Ovarian Cancer","authors":"Jiaojiao Lu, Shuai Zhen, Xu Li","doi":"10.2174/0115665232323373240905104033","DOIUrl":"https://doi.org/10.2174/0115665232323373240905104033","url":null,"abstract":"Background: Ovarian cancer is associated with a high mortality rate. Oxidative Phosphorylation (OXPHOS) is an active metabolic pathway in cancer; nevertheless, its role in ovarian cancer continues to be ambiguous. Therefore, the objective of this study was to identify the prognostic value of OXPHOS-related genes and the immune landscape in ovarian cancer. Methods: We obtained public ovarian cancer-related datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and recognized OXPHOS-related genes from the GeneCards database and literature. Cox regression analyses were conducted to identify prognostic OXPHOS-related genes and develop a prognostic nomogram based on the OXPHOS score and clinicopathological features of patients. Functional enrichment analyses were employed to identify related processes. Results: A 12-gene signature was identified to classify the ovarian cancer patients into high- and low-risk groups. The Immunophenoscore (IPS) was higher in the OXPHOS score-high group than in the OXPHOS score-low group, suggesting a better response to immune checkpoint inhibitors. Functional enrichment analyses unveiled that OXPHOS-related genes were considerably abundant in a series of immune processes. The calibration curves of the constructed prognostic nomograms at 1, 2, and 3 years exhibited strong concordance between the anticipated and observed survival probabilities of ovarian cancer patients. Conclusion: We have constructed a prognostic model containing 12 OXPHOS-related genes and demonstrated its strong predictive value in ovarian cancer patients. OXPHOS has been found to be closely linked to immune infiltration and the reaction to immunotherapy, which may contribute to improving individualized treatment and prognostic evaluation in ovarian cancer.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"19 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260000","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}