Current gene therapy最新文献

{"title":"Dysregulation of Transfer RNA-derived Small RNAs that Regulate Cell Activity and its Related Signaling Pathways in Human Cancers.","authors":"Tianyi Huang,&nbsp;Juan Du,&nbsp;Chujia Chen,&nbsp;Zhen Zheng,&nbsp;Shuai Fang,&nbsp;Kaitai Liu","doi":"10.2174/1566523223666230601102506","DOIUrl":"https://doi.org/10.2174/1566523223666230601102506","url":null,"abstract":"<p><p>tsRNAs are small noncoding RNAs that originate from tRNA cleavage and play important regulatory roles in gene expression, translation, transcription, and epigenetic modification. The dysregulation of tsRNAs in cancer disrupts gene expression and perturbs various cellular activities, including cell proliferation, apoptosis, migration, and invasion. Moreover, tsRNAs may influence cancer development by regulating related cell signaling pathways. In this review, we first examine the origins and classification of tsRNAs and their effects on tumor cell activity. To highlight the latest research progress of tsRNAs and signaling pathways, we summarize the possible mechanisms of tsRNAs in specific tumor-related signaling pathways, including the Wnt, TGFb1, MAPK, PI3K-AKT, Notch, and MDM2/p53 signaling pathways, that have been identified in recent research.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 4","pages":"291-303"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934944","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":"Reversal of Neuropsychiatric Comorbidities in an Animal Model of Temporal Lobe Epilepsy Following Systemic Administration of Dental Pulp Stem Cells and Bone Marrow Mesenchymal Stem Cells.","authors":"Sivapriya Senthilkumar,&nbsp;Krishnamoorthi Maiya,&nbsp;Nishta Kusum Jain,&nbsp;Mata Sundeep,&nbsp;Snehal Mangaonkar,&nbsp;Prajnya Prabhu,&nbsp;Kiranmai S Rai,&nbsp;Bindu M Kutty,&nbsp;Anandh Dhanushkodi","doi":"10.2174/1566523223666221027113723","DOIUrl":"https://doi.org/10.2174/1566523223666221027113723","url":null,"abstract":"<p><strong>Introduction: </strong>We aim to investigate whether timed systemic administration of dental pulp stem cells (DPSCs) or bone marrow mesenchymal stem cells (BM-MSCs) with status epilepticus (SE) induced blood-brain barrier (BBB) damage could facilitate the CNS homing of DPSCs/BM-MSCs and mitigate neurodegeneration, neuroinflammation and neuropsychiatric comorbidities in an animal model of Temporal Lobe epilepsy (TLE).</p><p><strong>Background: </strong>Cognitive impairments, altered emotional responsiveness, depression, and anxiety are the common neuropsychiatric co-morbidities observed in TLE patients. Mesenchymal stem cells (MSCs) transplantation has gained immense attention in treating TLE, as ~30% of patients do not respond to anti-epileptic drugs. While MSCs are known to cross the BBB, better CNS homing and therapeutic effects could be achieved when the systemic administration of MSC is timed with BBB damage following SE.</p><p><strong>Objectives: </strong>The objectives of the present study are to investigate the effects of systemic administration of DPSCs/BM-MSCs timed with BBB damage on CNS homing of DPSCs/BM-MSCs, neurodegeneration, neuroinflammation and neuropsychiatric comorbidities in an animal model of TLE.</p><p><strong>Methodology: </strong>We first assessed the BBB leakage following kainic acid-induced SE and timed the intravenous administration of DPSCs/BM-MSCs to understand the CNS homing/engraftment potential of DPSCs/BM-MSCs and their potential to mitigate neurodegeneration, neuroinflammation and neuropsychiatric comorbidities.</p><p><strong>Results: </strong>Our results revealed that systemic administration of DPSCs/BM-MSCs attenuated neurodegeneration, neuroinflammation, and ameliorated neuropsychiatric comorbidities. Three months following intravenous administration of DPSCs/BM-MSCs, we observed a negligible number of engrafted cells in the corpus callosum, sub-granular zone, and sub-ventricular zone.</p><p><strong>Conclusion: </strong>Thus, it is evident that functional recovery is still achievable despite poor engraftment of MSCs into CNS following systemic administration.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 3","pages":"198-214"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9808889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advancements in DNA Hairpin-based Fluorescent Probes.","authors":"Nikita Sharma,&nbsp;Debashree Debasish Das,&nbsp;Pooja A Chawla","doi":"10.2174/1566523223666230619150006","DOIUrl":"10.2174/1566523223666230619150006","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"368-370"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9672968","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":"Whole Exome Sequencing Identified Two Single Nucleotide Polymorphisms of Human Leukocyte Antigen-DRB5 in Familial Sarcoidosis in China.","authors":"Qian Zhang,&nbsp;Zuojun Xu,&nbsp;Hui Huang,&nbsp;Meijun Zhang","doi":"10.2174/1566523223666230119143501","DOIUrl":"https://doi.org/10.2174/1566523223666230119143501","url":null,"abstract":"<p><strong>Background: </strong>Sarcoidosis is a multisystem granulomatous disorder whose etiology is related to genetic and immunological factors. Familial aggregation and ethnic prevalence suggest a genetic predisposition and inherited susceptibility to sarcoidosis.</p><p><strong>Objective: </strong>This study aimed to identify suspected risk loci for familial sarcoidosis patients.</p><p><strong>Methods: </strong>We conducted whole exome sequencing on two sarcoidosis patients and five healthy family members in a Chinese family for a case-control study. The two sarcoidosis patients were siblings who showed chronic disease.</p><p><strong>Results: </strong>The Gene Ontology results showed single nucleotide polymorphisms in three genes, including human leukocyte antigen (<i>HLA)-DRB1, HLA-DRB5, and KIR2DL4</i>, associated with both 'antigen processing and presentation' and 'regulation of immune response.' Sanger sequencing verified two nonsynonymous mutations in <i>HLA-DRB5</i> (rs696318 and rs115817940) located on 6p21.3 in the major histocompatibility complex (MHC) class II beta 1 region. The structural model simulated on Prot- Param protein analysis by the Expert Protein Analysis System predicted that the hydropathy index changed at two mutation sites (rs696318: p.F96L, -1.844 to -1.656 and rs115817940: p.T106N, -0.322 to -0.633), which indicated the probability of changes in peptide-binding selectivity.</p><p><strong>Conclusion: </strong>Our results indicated that two nonsynonymous mutations of <i> HLA-DRB5</i> have been identified in two sarcoidosis siblings, while their healthy family members do not have the mutations. The two <i>HLA-DRB5</i> alleles may influence genetic susceptibility and chronic disease progression through peptide mutations on the MHC class II molecule among the two affected family members.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 3","pages":"215-227"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10583055","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, A Potential Therapeutic Tool for Neurological and Neuropsychiatric Disorders: Applications, Challenges and Future Perspective.","authors":"Shalini Mani,&nbsp;Divya Jindal,&nbsp;Manisha Singh","doi":"10.2174/1566523222666220328142427","DOIUrl":"https://doi.org/10.2174/1566523222666220328142427","url":null,"abstract":"<p><p>Neurological and neuropsychiatric disorders are the main risks for the health care system, exhibiting a huge socioeconomic load. The available range of pharmacotherapeutics mostly provides palliative consequences and fails to treat such conditions. The molecular etiology of various neurological and neuropsychiatric disorders is mostly associated with a change in genetic background, which can be inherited/triggered by other environmental factors. To address such conditions, gene therapy is considered a potential approach claiming a permanent cure of the disease primarily by deletion, silencing, or edition of faulty genes and by insertion of healthier genes. In gene therapy, vectors (viral/nonvial) play an important role in delivering the desired gene to a specific region of the brain. Targeted gene therapy has unraveled opportunities for the treatment of many neurological and neuropsychiatric disorders. For improved gene delivery, the current techniques mainly focus on designing a precise viral vector, plasmid transfection, nanotechnology, microRNA, and in vivo clustered regulatory interspaced short palindromic repeats (CRISPR)-based therapy. These latest techniques have great benefits in treating predominant neurological and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder, as well as rarer diseases. Nevertheless, all these delivery methods have their limitations, including immunogenic reactions, off-target effects, and a deficiency of effective biomarkers to appreciate the effectiveness of therapy. In this review, we present a summary of the current methods in targeted gene delivery, followed by the limitations and future direction of gene therapy for the cure of neurological and neuropsychiatric disorders.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 1","pages":"20-40"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9140122","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":"Amyotrophic Lateral Sclerosis Risk Genes and Suppressor.","authors":"Rupesh Kumar,&nbsp;Zubbair Malik,&nbsp;Manisha Singh,&nbsp;Rachna,&nbsp;Shalini Mani,&nbsp;Kalaiarasan Ponnusamy,&nbsp;Shazia Haider","doi":"10.2174/1566523223666221108113330","DOIUrl":"https://doi.org/10.2174/1566523223666221108113330","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to death by progressive paralysis and respiratory failure within 2-4 years of onset. About 90-95% of ALS cases are sporadic (sALS), and 5-10% are inherited through family (fALS). Though the mechanisms of the disease are still poorly understood, so far, approximately 40 genes have been reported as ALS causative genes. The mutations in some crucial genes, like SOD1, C9ORF72, FUS, and TDP-43, are majorly associated with ALS, resulting in ROS-associated oxidative stress, excitotoxicity, protein aggregation, altered RNA processing, axonal and vesicular trafficking dysregulation, and mitochondrial dysfunction. Recent studies show that dysfunctional cellular pathways get restored as a result of the repair of a single pathway in ALS. In this review article, our aim is to identify putative targets for therapeutic development and the importance of a single suppressor to reduce multiple symptoms by focusing on important mutations and the phenotypic suppressors of dysfunctional cellular pathways in crucial genes as reported by other studies.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 2","pages":"148-162"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9195542","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 Alzheimer and Parkinson Diseases.","authors":"Jasen F Saad,&nbsp;Fawzy A Saad","doi":"10.2174/1566523223666230419101023","DOIUrl":"https://doi.org/10.2174/1566523223666230419101023","url":null,"abstract":"<p><p>Alzheimer and Parkinson diseases are associated with cholinergic neuron loss and deterioration of bone mineral density. Gene therapy through either gene transfer, CRISPR gene editing, or CRISPR gene modulation holds the potential to cure Alzheimer and Parkinson diseases. The emerging role of weight-bearing exercise in the prevention of, and care for, osteoporosis, obesity, and diabetes has been previously recognized. Moreover, endurance exercise offers a viable alternative to reduce amyloid peptides deposits while increasing bone mineral density in Alzheimer and Parkinson patients. β-amyloid peptides, α-synuclein, and tau aggregates start building up two decades before the onset of Alzheimer and Parkinson diseases. Therefore, an early intervention program for the detection of these deposits is required to prevent or delay the onset of these diseases. This article spots light on the potential of gene therapy for Alzheimer and Parkinson diseases.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 3","pages":"163-169"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9750547","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 Cargoes Based on Viral Vector Delivery.","authors":"Kenneth Lundstrom","doi":"10.2174/1566523222666220921112753","DOIUrl":"https://doi.org/10.2174/1566523222666220921112753","url":null,"abstract":"<p><p>Viral vectors have been proven useful in a broad spectrum of gene therapy applications due to their possibility to accommodate foreign genetic material for both local and systemic delivery. The wide range of viral vectors has enabled gene therapy applications for both acute and chronic diseases. Cancer gene therapy has been addressed by the delivery of viral vectors expressing anti-tumor, toxic, and suicide genes for the destruction of tumors. Delivery of immunostimulatory genes such as cytokines and chemokines has also been applied for cancer therapy. Moreover, oncolytic viruses specifically replicating in and killing tumor cells have been used as such for tumor eradication or in combination with tumor killing or immunostimulatory genes. In a broad meaning, vaccines against infectious diseases and various cancers can be considered gene therapy, which has been highly successful, not the least for the development of effective COVID-19 vaccines. Viral vector-based gene therapy has also demonstrated encouraging and promising results for chronic diseases such as severe combined immunodeficiency (SCID), muscular dystrophy, and hemophilia. Preclinical gene therapy studies in animal models have demonstrated proof-of-concept for a wide range of disease indications. Clinical evaluation of drugs and vaccines in humans has showed high safety levels, good tolerance, and therapeutic efficacy. Several gene therapy drugs such as the adenovirus-based drug Gendicine® for non-small-cell lung cancer, the reovirus-based drug Reolysin® for ovarian cancer, lentivirus-based treatment of SCID-X1 disease, and the rhabdovirus-based vaccine Ervebo against Ebola virus disease, and adenovirus-based vaccines against COVID-19 have been developed.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 2","pages":"111-134"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9494119","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":"Current Landscape and Emerging Opportunities of Gene Therapy with Non-viral Episomal Vectors.","authors":"Safir Ullah Khan,&nbsp;Munir Ullah Khan,&nbsp;Muhammad Imran Khan,&nbsp;Fadia Kalsoom,&nbsp;Aqeela Zahra","doi":"10.2174/1566523222666221004100858","DOIUrl":"https://doi.org/10.2174/1566523222666221004100858","url":null,"abstract":"<p><p>Gene therapy has proven to be extremely beneficial in the management of a wide range of genetic disorders for which there are currently no or few effective treatments. Gene transfer vectors are very significant in the field of gene therapy. It is possible to attach a non-viral attachment vector to the donor cell chromosome instead of integrating it, eliminating the negative consequences of both viral and integrated vectors. It is a safe and optimal express vector for gene therapy because it does not cause any adverse effects. However, the modest cloning rate, low expression, and low clone number make it unsuitable for use in gene therapy. Since the first generation of non-viral attachment episomal vectors was constructed, various steps have been taken to regulate their expression and stability, such as truncating the MAR element, lowering the amount of CpG motifs, choosing appropriate promoters and utilizing regulatory elements. This increases the transfection effectiveness of the non-viral attachment vector while also causing it to express at a high level and maintain a high level of stability. A vector is a genetic construct commonly employed in gene therapy to treat various systemic disorders. This article examines the progress made in the development of various optimization tactics for nonviral attachment vectors and the future applications of these vectors in gene therapy.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 2","pages":"135-147"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9494596","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":"Proteomic Analyses Reveal Functional Pathways and Potential Targets in Pediatric Hydrocephalus.","authors":"Yiwen Ju,&nbsp;Zhenling Wan,&nbsp;Qin Zhang,&nbsp;Si Li,&nbsp;Bingshu Wang,&nbsp;Jianmin Qiu,&nbsp;Shaojiang Zheng,&nbsp;Shuo Gu","doi":"10.2174/1566523223666230613144056","DOIUrl":"10.2174/1566523223666230613144056","url":null,"abstract":"<p><strong>Introduction: </strong>Hydrocephalus is a common pediatric disorder of cerebral spinal fluid physiology resulting in abnormal expansion of the cerebral ventricles. However, the underlying molecular mechanisms remain unknown.</p><p><strong>Methods: </strong>We performed proteomic analyses of cerebrospinal fluid (CSF) from 7 congenital hydrocephalus and 5 arachnoid cyst patients who underwent surgical treatment. Differentially expressed proteins (DEPs) were identified by label-free Mass Spectrometry followed by differential expression analysis. The GO and GSEA enrichment analysis was performed to explore the cancer hallmark pathways and immune-related pathways affected by DEPs. Then, network analysis was applied to reveal the location of DEPs in the human protein-protein interactions (PPIs) network. Potential drugs for hydrocephalus were identified based on drug-target interaction.</p><p><strong>Results: </strong>We identified 148 up-regulated proteins and 82 down-regulated proteins, which are potential biomarkers for clinical diagnosis of hydrocephalus and arachnoid cyst. Functional enrichment analysis revealed that the DEPs were significantly enriched in the cancer hallmark pathways and immunerelated pathways. In addition, network analysis uncovered that DEPs were more likely to be located in the central regions of the human PPIs network, suggesting DEPs may be proteins that play important roles in human PPIs. Finally, we calculated the overlap of drug targets and the DEPs based on drugtarget interaction to identify the potential therapeutic drugs of hydrocephalus.</p><p><strong>Conclusion: </strong>The comprehensive proteomic analyses provided valuable resources for investigating the molecular pathways in hydrocephalus, and uncovered potential biomarkers for clinical diagnosis and therapy.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"400-409"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9790896","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}