Current gene therapy最新文献

{"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":"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}

{"title":"Development of Cell and Gene Therapies for Clinical Use in the US and EU: Summary of Regulatory Guidelines","authors":"Anand Rotte","doi":"10.2174/0115665232306205240419091414","DOIUrl":"https://doi.org/10.2174/0115665232306205240419091414","url":null,"abstract":"Recent decades have seen advancements in the management and treatment of difficult-- to-treat diseases such as cancer. A special class of therapeutics called cell and gene therapy has been introduced in the past 10 years. Cell and gene therapy products have strengthened the treatment options for life-threatening diseases with unmet clinical needs and also provided the possibility of a potential cure for the disease in some of the patients. Cell and gene therapy products are gaining recognition, and the interest in clinical development of cell and gene therapy products is increasing. Moreover, as the class of cell and gene therapy products is relatively new, there is a limited regulatory experience in the development, and the developers of the cell and gene therapy products can often be puzzled with an array of questions on regulations. The current review intends to provide a basic understanding of regulatory guidelines from the FDA and EMA that are applicable to cell and gene therapy products. Essentials such as which office is responsible for the evaluation of applications, which regulatory class/pathway is appropriate for development, and what are the quality, nonclinical and clinical studies that are needed to support the application are discussed in the article. In addition, a summary of regulatory designations and the post-approval requirements, such as Risk Evaluation and Mitigation Strategies (REMS) and long-term follow- up, is included in the article. Developers (referred to as ‘sponsors’ in this article) of cell and gene therapies can use the respective guidance documents and other specific review articles cited in this review for detailed information on the topics.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"33 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Non-coding RNAs on the Radiotherapy Sensitivity and Resistance in Cancer Cells","authors":"Fatemeh Jalali-Zefrei, Seyed Mehdi Mousavi, Kourosh Delpasand, Mohammad Shourmij, Soghra Farzipour","doi":"10.2174/0115665232301727240422092311","DOIUrl":"https://doi.org/10.2174/0115665232301727240422092311","url":null,"abstract":": Radiotherapy (RT) is an integral part of treatment management in cancer patients. However, one of the limitations of this treatment method is the resistance of cancer cells to radiotherapy. These restrictions necessitate the introduction of modalities for the radiosensitization of cancer cells. It has been shown that Noncoding RNAs (ncRNAs), along with modifiers, can act as radiosensitivity and radioresistant regulators in a variety of cancers by affecting double strand break (DSB), wnt signaling, glycolysis, irradiation induced apoptosis, ferroptosis and cell autophagy. This review will provide an overview of the latest research on the roles and regulatory mechanisms of ncRNA after RT in in vitro and preclinical research.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"20 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810447","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":"Evolution of Prime Editing Systems: Move Forward to the Treatment of Hereditary Diseases","authors":"Olga V. Volodina, Anastasia R. Fabrichnikova, Arina A. Anuchina, Olesya S. Mishina, Alexander V. Lavrov, Svetlana A. Smirnikhina","doi":"10.2174/0115665232295117240405070809","DOIUrl":"https://doi.org/10.2174/0115665232295117240405070809","url":null,"abstract":": The development of gene therapy using genome editing tools recently became relevant. With the invention of programmable nucleases, it became possible to treat hereditary diseases due to introducing targeted double strand break in the genome followed by homology directed repair (HDR) or non-homologous end-joining (NHEJ) reparation. CRISPR-Cas9 is more efficient and easier to use in comparison with other programmable nucleases. To improve the efficiency and safety of this gene editing tool, various modifications CRISPR-Cas9 basis were created in recent years, such as prime editing – in this system, Cas9 nickase is fused with reverse transcriptase and guide RNA, which contains a desired correction. Prime editing demonstrates equal or higher correction efficiency as HDR-mediated editing and much less off-target effect due to inducing nick. There are several studies in which prime editing is used to correct mutations in which researchers reported little or no evidence of off-target effects. The system can also be used to functionally characterize disease variants. However, prime editing still has several limitations that could be further improved. The effectiveness of the method is not yet high enough to apply it in clinical trials. Delivery of prime editors is also a big challenge due to their size. In the present article, we observe the development of the platform, and discuss the candidate proteins for efficiency enhancing, main delivery methods and current applications of prime editing.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"44 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586457","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":"Efficacy and Safety of Pembrolizumab Monotherapy or Combined Therapy in Patients with Metastatic Triple-negative Breast Cancer: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","authors":"Mahmood Araghi, Farshad Gharebakhshi, Fatemeh Faramarzi, Alireza mafi, Tahoora Mousavi, Mina Alimohammadi, Hussein Soleimantabar","doi":"10.2174/0115665232283880240301035621","DOIUrl":"https://doi.org/10.2174/0115665232283880240301035621","url":null,"abstract":"Background: Metastatic Triple-negative Breast Cancer (mTNBC) is the most aggressive form of breast cancer, with a greater risk of metastasis and recurrence. Research studies have published in-depth analyses of the advantages and disadvantages of pembrolizumab, and early data from numerous trials suggests that patients with mTNBC have had remarkable outcomes. This meta-analysis compares the data from numerous relevant studies in order to evaluate the safety and efficacy of pembrolizumab monotherapy or combination therapies for mTNBC. Methods: To identify eligible RCTs, a thorough literature search was carried out using electronic databases. CMA software was utilized to perform heterogeneity tests using fixed and random-effects models. Results: According to our pooled data, the median Progression-free Survival (PFS) was 2.66 months, and the median overall survival (OS) was 12.26 months. Furthermore, by comparing efficacy indicators between PD-L1–positive and PD-L1–negative groups, a correlation was found between the overexpression of PD-L1 with OS, PFS, and ORR. Patients with PD-L1-positive tumors had a higher response rate, with an ORR of 21.1%, compared to the patients with PD-L1-negative tumors. The ORR for first-line immunotherapy was higher than that of ≥second-line immunotherapy. In addition, pembrolizumab plus combination treatment resulted in a pooled incidence of immune-related adverse events of 22.7%. Conclusion: A modest response to pembrolizumab monotherapy was detected in the mTNBC patients. Furthermore, a better outcome from pembrolizumab treatment may be predicted by PD-L1-- positive status, non-liver/lung metastases, combination therapy, and first-line immunotherapy. Pembrolizumab, in combination with chemotherapy, may be more beneficial for patients whose tumors are PD-L1 positive.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"290 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140115293","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 Functions and Application Prospects of Hepatocyte Growth Factor in Reproduction","authors":"Xin Mi, Caiyi Chen, Chen Feng, Yingying Qin, Zi-Jiang Chen, Yajuan Yang, Shidou Zhao","doi":"10.2174/0115665232291010240221104445","DOIUrl":"https://doi.org/10.2174/0115665232291010240221104445","url":null,"abstract":": Hepatocyte growth factor (HGF) is expressed in multiple systems and mediates a variety of biological activities, such as mitosis, motility, and morphogenesis. A growing number of studies have revealed the expression patterns and functions of HGF in ovarian and testicular physiology from the prenatal to the adult stage. HGF regulates folliculogenesis and steroidogenesis by modulating the functions of theca cells and granulosa cells in the ovary. It also mediates somatic cell proliferation and steroidogenesis, thereby affecting spermatogenesis in males. In addition to its physiological effects on the reproductive system, HGF has shown advantages in preclinical studies over recent years for the treatment of male and female infertility, particularly in women with premature ovarian insufficiency. This review aims to summarize the pleiotropic functions of HGF in the reproductive system and to provide prospects for its clinical application.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"170 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140008252","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":"Effect of Bovine Lactoferrin Treatment on Iron Homeostasis and Gene Expression Changes in Multiple Organ Dysfunctions During Wound Healing Process in Rats","authors":"Ahmet Sarper Bozkurt, Şenay Görücü Yılmaz","doi":"10.2174/0115665232279426240217174738","DOIUrl":"https://doi.org/10.2174/0115665232279426240217174738","url":null,"abstract":"Background:: Injury systemically disrupts the homeostatic balance and can cause organ failure. LF mediates both iron-dependent and iron-independent mechanisms, and the role of LF in regulating iron homeostasis is vital in terms of metabolism. Objectives:: In this study, we evaluated the organ-level effect and gene expression change of bLf in the cutaneous repair process. Materials and Methods:: An excisional full-thickness skin defect (FTSD) wound model was created in male Sprague Dawley rats (180-250 g) (n = 48) fed a high-fat diet (HFD) and the PHGPx, SLC7A11 and SLC40A1 genes and iron metabolism were evaluated. The animals were randomly divided into 6 groups: 1- Control, 2- bLf (200 mg/kg/day, oral), 3- FTSD (12 mm in diameter, dorsal), 4- HFD + bLf, 5- HFD + FTSD, 6- HFD + FTSD + bLf. Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Gene expression analysis was performed with qPCR. Results:: Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Prussian blue reactions were detected in the kidney. PHPGx and SLC7A11 genes in kidney and liver tissue were statistically significant (P &lt; 0.05) except for the SLC40A1 gene (P &gt; 0.05). Expression changes of the three genes were not statistically significant in analyses of rat intestinal tissue (P = 0.057). Conclusion:: In the organ-level ferroptotic damage mechanism triggered by wound formation. BLf controls the expression of three genes and manages iron deposition in these three tissues. In addition, it suppressed the increase in iron that would drive the cell to ferroptosis and anemia caused by inflammation, thereby eliminating iron deposition in the tissues.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"15 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139952682","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":"Biogenesis and Function of circRNAs in Pulmonary Fibrosis","authors":"Songzi Zhang, Wenjie Hu, Changjun Lv, Xiaodong Song","doi":"10.2174/0115665232284076240207073542","DOIUrl":"https://doi.org/10.2174/0115665232284076240207073542","url":null,"abstract":": Pulmonary fibrosis is a class of fibrosing interstitial lung diseases caused by many pathogenic factors inside and outside the lung, with unknown mechanisms and without effective treatment. Therefore, a comprehensive understanding of the molecular mechanism implicated in pulmonary fibrosis pathogenesis is urgently needed to develop new and effective measures. Although circRNAs have been widely acknowledged as new contributors to the occurrence and development of diseases, only a small number of circRNAs have been functionally characterized in pulmonary fibrosis. Here, we systematically review the biogenesis and functions of circRNAs and focus on how circRNAs participate in pulmonary fibrogenesis by influencing various cell fates. Meanwhile, we analyze the current exploration of circRNAs as a diagnostic biomarker, vaccine, and therapeutic target in pulmonary fibrosis and objectively discuss the challenges of circRNA-based therapy for pulmonary fibrosis. We hope that the review of the implication of circRNAs will provide new insights into the development circRNA-based approaches to treat pulmonary fibrosis.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"82 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770762","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}