Current gene therapy最新文献

{"title":"HCST Expression Distinguishes Immune-hot and Immune-cold Subtypes in Pancreatic Ductal Adenocarcinoma","authors":"Boyi Ma, Dai-Jun Zhang, Yabin Hu, Xianghan Chen, Ruining Gong, Ke Lei, Qian Yu, He Ren","doi":"10.2174/1566523223666230720101531","DOIUrl":"10.2174/1566523223666230720101531","url":null,"abstract":"<p><strong>Introduction: </strong>Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent malignancy of the pancreas, and the incidence of this disease is approximately equivalent to the mortality rate. Immunotherapy has made a remarkable breakthrough in numerous cancers, while its efficacy in PDAC remains limited due to the immunosuppressive microenvironment. Immunotherapy efficacy is highly correlated with the abundance of immune cells, particularly cytotoxic T cells. Therefore, molecular classifier is needed to identify relatively hot tumors that may benefit from immunotherapy.</p><p><strong>Method: </strong>In this study, we carried out a transcriptome analysis of 145 pancreatic tumors to define the underlying immune regulatory mechanism driving the PDAC immunosuppressive microenvironment. The immune subtype was identified by consensus clustering, and the underlying PDAC immune activation mechanism was thoroughly examined using single sample gene set enrichment analysis (ssGSEA). Area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the accuracy of the molecular classifier in differentiating immunological subgroups of PDAC.5.</p><p><strong>Result: </strong>The protein level of molecular classifier was verified by immunohistochemistry in human PDAC tissue. Immune-hot tumors displayed higher levels of immune cell infiltration and immune checkpoint, in line with enriched immune escape pathways. Hematopoietic cell signal transducer (HCST), a molecular classifier used to differentiate immunological subtypes of PDAC, has shown a substantial link with the expression levels of cytotoxic markers, such as CD8A and CD8B. At the single cell level, we found that HCST was predominantly expressed in CD8T cells. By immunohistochemistry and survival analysis, we further demonstrated the prognostic value of HCST in PDAC.</p><p><strong>Conclusion: </strong>We identified HCST as a molecular classifier to distinguish PDAC immune subtypes, which may be useful for early diagnosis and targeted therapy of PDAC.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"62-71"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9836418","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 Important Genes Associated with the Development of Atherosclerosis.","authors":"Stanislav Kotlyarov","doi":"10.2174/1566523223666230330091241","DOIUrl":"10.2174/1566523223666230330091241","url":null,"abstract":"<p><p>Atherosclerosis is one of the most important medical problems due to its prevalence and significant contribution to the structure of temporary and permanent disability and mortality. Atherosclerosis is a complex chain of events occurring in the vascular wall over many years. Disorders of lipid metabolism, inflammation, and impaired hemodynamics are important mechanisms of atherogenesis. A growing body of evidence strengthens the understanding of the role of genetic and epigenetic factors in individual predisposition and development of atherosclerosis and its clinical outcomes. In addition, hemodynamic changes, lipid metabolism abnormalities, and inflammation are closely related and have many overlapping links in regulation. A better study of these mechanisms may improve the quality of diagnosis and management of such patients.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"29-45"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9590296","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":"ZNF695, A Potential Prognostic Biomarker, Correlates with Im mune Infiltrates in Cervical Squamous Cell Carcinoma and Endoce rvical Adenocarcinoma: Bioinformatic Analysis and Experimental Verification.","authors":"Xiaojuan Ding, Ailing Wan, Xin Qi, Ke'er Jiang, Zhao Liu, Buze Chen","doi":"10.2174/0115665232285216240228071244","DOIUrl":"10.2174/0115665232285216240228071244","url":null,"abstract":"<p><strong>Background: </strong>The role of Zinc Finger Protein 695 (ZNF695) is unclear in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).</p><p><strong>Objective: </strong>The objective of this study was to conduct a comprehensive analysis and experimental validation of ZNF695 in CESC.</p><p><strong>Methods: </strong>The study investigated the expression of ZNF695 in both pan-cancer and CESC, utilizing data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The present study investigated the association between ZNF695 expression levels and clinical characteristics, as well as prognosis, in patients with CESC. The study explored potential regulatory networks involving ZNF695, including its association with immune infiltration, immune score, stemness index based on mRNA expression (mRNAsi), and drug sensitivity in CESC. We explored the expression of ZNF695 in CESC single cells. ZNF695 expression was validated using GSE29570.</p><p><strong>Results: </strong>ZNF695 was found to be aberrantly expressed in pan-cancer and CESC. There was a significant correlation observed between an elevated level of ZNF695 expression in patients with CESC and histological grade (p = 0.017). Furthermore, a strong association was found between high ZNF695 expression in CESC patients and poorer overall survival (OS) (HR: 1.87; 95% CI: 1.17-3.00; p = 0.009), Progression-free Survival (PFS) (HR: 1.86; 95% CI: 1.16-2.98; p = 0.010), and Disease-specific Survival (DSS) (HR: 1.98; 95% CI: 1.15-3.42; p = 0.014). The expression of ZNF695 in CESC patients (p = 0.006) was identified as an independent prognostic determinant. ZNF695 was associated with steroid hormone biosynthesis, oxidative phosphorylation, and so on. ZNF695 expression correlated with immune infiltration, immune score, and mRNAsi in CESC. ZNF695 expression significantly and negatively correlated with AICA ribonucleotide, BIX02189, QL-XI-92, STF-62247, and SNX-2112 in CESC. ZNF695 gene was upregulated in CESC tissues and cell lines. ZNF695 was significantly upregulated in the CESC cell lines.</p><p><strong>Conclusion: </strong>ZNF695 may be a potential prognostic biomarker and immunotherapeutic target for CESC patients.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"441-452"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027606","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":"RNA Interference and Neuromuscular Diseases: A Focus on Hereditary Transthyretin Amyloidosis.","authors":"Marco Ceccanti, Maurizio Inghilleri","doi":"10.2174/1566523223666230913110011","DOIUrl":"10.2174/1566523223666230913110011","url":null,"abstract":"<p><p>Neuromuscular diseases are severe disorders affecting the peripheral nervous system, usually driving to death in a limited time. Many new drugs, through RNA-interference technology, are revolutionizing the prognosis and quality of life for these patients. Nevertheless, given the increased life expectancy, some new issues and phenotypes are expected to be revealed. In the transthyretin-mediated hereditary amyloidosis (ATTR-v, \"v\" for \"variant\"), the RNA interference was demonstrated to effectively reduce the hepatic synthesis of transthyretin, with a significant increase in disease progression in terms of polyneuropathy and cardiomyopathy. The increased life expectancy could promote the involvement of organs where the extra-hepatic transthyretin is deposited, such as the brain and eye, which are probably not targeted by the available treatments. All these issues are discussed in this editorial.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"6-7"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10245574","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":"Applications of Scaffolds in Tissue Engineering: Current Utilization and Future Prospective.","authors":"Shikha Yadav, Javed Khan, Agrima Yadav","doi":"10.2174/0115665232262167231012102837","DOIUrl":"10.2174/0115665232262167231012102837","url":null,"abstract":"<p><p>Current regenerative medicine tactics focus on regenerating tissue structures pathologically modified by cell transplantation in combination with supporting scaffolds and biomolecules. Natural and synthetic polymers, bioresorbable inorganic and hybrid materials, and tissue decellularized were deemed biomaterials scaffolding because of their improved structural, mechanical, and biological abilities.Various biomaterials, existing treatment methodologies and emerging technologies in the field of Three-dimensional (3D) and hydrogel processing, and the unique fabric concerns for tissue engineering. A scaffold that acts as a transient matrix for cell proliferation and extracellular matrix deposition, with subsequent expansion, is needed to restore or regenerate the tissue. Diverse technologies are combined to produce porous tissue regenerative and tailored release of bioactive substances in applications of tissue engineering. Tissue engineering scaffolds are crucial ingredients. This paper discusses an overview of the various scaffold kinds and their material features and applications. Tabulation of the manufacturing technologies for fabric engineering and equipment, encompassing the latest fundamental and standard procedures.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"94-109"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421509","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":"Precision Genome Editing Techniques in Gene Therapy: Current State and Future Prospects.","authors":"Kuldeep Singh, Bharat Bhushan, Sunil Kumar, Supriya Singh, Romulo R Macadangdang, Ekta Pandey, Ajit Kumar Varma, Shivendra Kumar","doi":"10.2174/0115665232279528240115075352","DOIUrl":"10.2174/0115665232279528240115075352","url":null,"abstract":"<p><p>Precision genome editing is a rapidly evolving field in gene therapy, allowing for the precise modification of genetic material. The CRISPR and Cas systems, particularly the CRISPRCas9 system, have revolutionized genetic research and therapeutic development by enabling precise changes like single-nucleotide substitutions, insertions, and deletions. This technology has the potential to correct disease-causing mutations at their source, allowing for the treatment of various genetic diseases. Programmable nucleases like CRISPR-Cas9, transcription activator-like effector nucleases (TALENs), and zinc finger nucleases (ZFNs) can be used to restore normal gene function, paving the way for novel therapeutic interventions. However, challenges, such as off-target effects, unintended modifications, and ethical concerns surrounding germline editing, require careful consideration and mitigation strategies. Researchers are exploring innovative solutions, such as enhanced nucleases, refined delivery methods, and improved bioinformatics tools for predicting and minimizing off-target effects. The prospects of precision genome editing in gene therapy are promising, with continued research and innovation expected to refine existing techniques and uncover new therapeutic applications.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"377-394"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520285","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":"Duchenne Muscular Dystrophy Gene Therapy.","authors":"Fawzy A Saad, Jasen F Saad, Gabriele Siciliano, Luciano Merlini, Corrado Angelini","doi":"10.2174/1566523223666221118160932","DOIUrl":"10.2174/1566523223666221118160932","url":null,"abstract":"<p><p>Duchenne and Becker muscular dystrophies are allelic X-linked recessive neuromuscular diseases affecting both skeletal and cardiac muscles. Therefore, owing to their single X chromosome, the affected boys receive pathogenic gene mutations from their unknowing carrier mothers. Current pharmacological drugs are palliative that address the symptoms of the disease rather than the genetic cause imbedded in the <i>Dystrophin</i> gene DNA sequence. Therefore, alternative therapies like gene drugs that could address the genetic cause of the disease at its root are crucial, which include gene transfer/implantation, exon skipping, and gene editing. Presently, it is possible through genetic reprogramming to engineer AAV vectors to deliver certain therapeutic cargos specifically to muscle or other organs regardless of their serotype. Similarly, it is possible to direct the biogenesis of exosomes to carry gene editing constituents or certain therapeutic cargos to specific tissue or cell type like brain and muscle. While autologous exosomes are immunologically inert, it is possible to camouflage AAV capsids, and lipid nanoparticles to evade the immune system recognition. In this review, we highlight current opportunities for Duchenne muscular dystrophy gene therapy, which has been known thus far as an incurable genetic disease. This article is a part of Gene Therapy of Rare Genetic Diseases thematic issue.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"17-28"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9328449","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":"Exosome miR-30a-5p Regulates Glomerular Endothelial Cells' EndMT and Angiogenesis by Modulating Notch1/VEGF Signaling Pathway.","authors":"Yaxian Ning, Xiaochun Zhou, Gouqin Wang, Lili Zhang, Jianqin Wang","doi":"10.2174/0115665232258527230919071328","DOIUrl":"10.2174/0115665232258527230919071328","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN) is one of the microvascular complications of diabetes. Endothelial-mesenchymal transition (EndMT) and endothelial damage lead to abnormal angiogenesis in DN.</p><p><strong>Objectives: </strong>This study aimed to investigate the role of exosome miR-30a-5p in high glucose (HG)-induced glomerular endothelial cells (GECs) dysfunction and explore the underlying mechanisms.</p><p><strong>Methods: </strong>GECs were cultured in normal glucose (5.5 mM) and HG (30 mM) conditions. The recipient GECs were transfected with exosome or miR-30a-5p mimic/inhibitor and then detected by using CCK-8 and flow cytometry assay. Luciferase analysis was used to verify miR-30a-5p acted on notch homolog protein 1 (Notch1). RT-qPCR and Western blot were used to detect the expression of VE-cadherin, α-SMA, vascular endothelial growth factor (VEGF) and Notch1. In vivo, exosome miR-30a-5p was administered to DN mice, and periodic acid-Schiff (PAS) staining, UTP levels, and HbA1c levels were measured.</p><p><strong>Results: </strong>The expression of miR-30a-5p was downregulated in HG-treated GECs. Exosome miR-30a-5p significantly promoted cell proliferation, and migration and reduced apoptosis of GECs under HG conditions. MiR-30a-5p directly targeted the 3-UTR region of Notch1. Exosome miR-30a-5p reduced the expression levels of Notch1 and VEGF, both at mRNA and protein levels. Furthermore, exosome miR-30a-5p inhibited HG-induced EndMT, as evidenced by increased VE-cadherin and reduced α-SMA. In vivo studies demonstrated that exosome miR-30a-5p reduced serum HbA1c levels and 24-hour urine protein quantification.</p><p><strong>Conclusion: </strong>This study provides evidence that exosome miR-30a-5p suppresses EndMT and abnormal angiogenesis of GECs by modulating the Notch1/VEGF signaling pathway. These findings suggest that exosome miR-30a-5p could be a potential therapeutic strategy for the treatment of DN.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"159-177"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41106454","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 Therapy for Rare Genetic Diseases.","authors":"Kenneth Lundstrom, Evangelia Yannaki, Janice Chou, Fawzy A Saad","doi":"10.2174/1566523223666230320120839","DOIUrl":"10.2174/1566523223666230320120839","url":null,"abstract":"","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"4-5"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9265457","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":"FIGNL1 Promotes Hepatocellular Carcinoma Formation <i>via</i> Remodeling ECM-receptor Interaction Pathway Mediated by HMMR.","authors":"Jiabei Wang, Linmao Sun, Yao Liu, Yunguang Zhang","doi":"10.2174/0115665232274223231017052707","DOIUrl":"10.2174/0115665232274223231017052707","url":null,"abstract":"<p><strong>Background: </strong>The development of novel biomarkers is crucial for the treatment of HCC. In this study, we investigated a new molecular therapeutic target for HCC. Fidgetin-like 1 (FIGNL1) has been reported to play a vital role in lung adenocarcinoma. However, the potential function of FIGNL1 in HCC is still unknown.</p><p><strong>Objective: </strong>This study aims to investigate the key regulatory mechanisms of FIGNL1 in the formation of HCC.</p><p><strong>Methods: </strong>The regulatory effect of FIGNL1 on HCC was studied by lentivirus infection. <i>In vitro</i>, the effects of FIGNL1 on the proliferation, migration and apoptosis of cells were investigated by CCK8, colony formation assay, transwell and flow cytometry. Meanwhile, the regulation of FIGNL1 on HCC formation <i>in vivo</i> was studied by subcutaneous transplanted tumors. In addition, using transcriptome sequencing technology, we further explored the specific molecular mechanism of FIGNL1 regulating the formation of HCC.</p><p><strong>Results: </strong>Functionally, we demonstrated that FIGNL1 knockdown significantly inhibited HCC cell proliferation, migration and promoted cell apoptosis <i>in vitro</i>. Similarly, the knockdown of FIGNL1 meaningfully weakened hepatocarcinogenesis in nude mice. Transcriptome sequencing revealed that FIGNL1 affected the expression of genes involved in extracellular matrix-receptor (ECM-receptor) interaction pathway, such as hyaluronan mediated motility receptor (HMMR). Further validation found that overexpression of HMMR based on knockdown FIGNL1 can rescue the expression abundance of related genes involved in the ECM-receptor interaction pathway.</p><p><strong>Conclusion: </strong>Our study revealed that FIGNL1 could modulate the ECM-receptor interaction pathway through the regulation of HMMR, thus regulating the formation of HCC.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"249-263"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11071652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479127","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}