Current gene therapyPub Date : 2024-01-01DOI: 10.2174/0115665232283842240102073002
Raman Kumar Tripathi, Lav Goyal, Shamsher Singh
{"title":"Potential Therapeutic Approach using Aromatic l-amino Acid Decarboxylase and Glial-derived Neurotrophic Factor Therapy Targeting Putamen in Parkinson's Disease.","authors":"Raman Kumar Tripathi, Lav Goyal, Shamsher Singh","doi":"10.2174/0115665232283842240102073002","DOIUrl":"10.2174/0115665232283842240102073002","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative illness characterized by specific loss of dopaminergic neurons, resulting in impaired motor movement. Its prevalence is twice as compared to the previous 25 years and affects more than 10 million individuals. Lack of treatment still uses levodopa and other options as disease management measures. Treatment shifts to gene therapy (GT), which utilizes direct delivery of specific genes at the targeted area. Therefore, the use of aromatic L-amino acid decarboxylase (AADC) and glial-derived neurotrophic factor (GDNF) therapy achieves an effective control to treat PD. Patients diagnosed with PD may experience improved therapeutic outcomes by reducing the frequency of drug administration while utilizing provasin and AADC as dopaminergic protective therapy. Enhancing the enzymatic activity of tyrosine hydroxylase (TH), glucocorticoid hormone (GCH), and AADC in the striatum would be useful for external L-DOPA to restore the dopamine (DA) level. Increased expression of glutamic acid decarboxylase (GAD) in the subthalamic nucleus (STN) may also be beneficial in PD. Targeting GDNF therapy specifically to the putaminal region is clinically sound and beneficial in protecting the dopaminergic neurons. Furthermore, preclinical and clinical studies supported the role of GDNF in exhibiting its neuroprotective effect in neurological disorders. Another Ret receptor, which belongs to the tyrosine kinase family, is expressed in dopaminergic neurons and sounds to play a vital role in inhibiting the advancement of PD. GDNF binding on those receptors results in the formation of a receptor-ligand complex. On the other hand, venous delivery of recombinant GDNF by liposome-based and encapsulated cellular approaches enables the secure and effective distribution of neurotrophic factors into the putamen and parenchyma. The current review emphasized the rate of GT target GDNF and AADC therapy, along with the corresponding empirical evidence.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"278-291"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680755","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}
Zhiwei Miao, Mingjia Gu, Faisal Raza, Hajra Zafar, Jianyi Huang, Yuhang Yang, Muhammad Sulaiman, Jing Yan, Yi Xu
{"title":"Isoliquiritin Ameliorates Ulcerative Colitis in Rats through Caspase 3/HMGB1/TLR4 Dependent Signaling Pathway.","authors":"Zhiwei Miao, Mingjia Gu, Faisal Raza, Hajra Zafar, Jianyi Huang, Yuhang Yang, Muhammad Sulaiman, Jing Yan, Yi Xu","doi":"10.2174/1566523223666230731115236","DOIUrl":"10.2174/1566523223666230731115236","url":null,"abstract":"<p><strong>Background: </strong>Isoliquiritin belongs to flavanol glycosides and has a strong antiinflammatory activity. This study sought to investigate the anti-inflammatory effect of isoliquiritin and its underlying mechanism.</p><p><strong>Methods: </strong>The inflammatory (trinitro-benzene-sulfonic acid-TNBS-induced ulcerative colitis (UC)) model was established to ascertain the effect of isoliquiritin on the caspase-3/HMGB1/TLR4 pathway in rats. We also explored its protective effect on intestinal inflammation and its underlying mechanism using the LPS-induced inflammation model of Caco-2 cells. Besides, Deseq2 was used to analyze UCassociated protein levels.</p><p><strong>Results: </strong>Isoliquiritin treatment significantly attenuated shortened colon length (induced by TNBS), disease activity index (DAI) score, and body weight loss in rats. A decrease in the levels of inflammatory mediators (IL-1β, I IL-4, L-6, IL-10, PGE2, and TNF-α), coupled with malondialdehyde (MDA) and superoxide dismutase (SOD), was observed in colon tissue and serum of rats after they have received isoliquiritin. Results of techniques (like western blotting, real-time PCR, immunohistochemistry, and immunofluorescence-IF) demonstrated the potential of isoliquiritin to decrease expressions of key genes in the TLR4 downstream pathways, viz., MyD88, IRAK1, TRAF6, NF-κB, p38, and JNK at mRNA and protein levels as well as inhibit HMGB1 expression, which is the upstream ligand of TLR4. Bioinformational analysis showed enteritis to be associated with a high expression of HMGB1, TLR4, and caspase-3.</p><p><strong>Conclusion: </strong>Isoliquiritin could reduce intestinal inflammation and mucosal damage of TNBS-induced colitis in rats with a certain anti-UC effect. Meanwhile, isoliquiritin treatment also inhibited the expression of HMGB1, TLR4, and MyD88 in LPS-induced Caco-2 cells. These results indicated that isoliquiritin could ameliorate UC through the caspase-3/HMGB1/TLR4-dependent signaling pathway.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"73-92"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9912083","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}
Current gene therapyPub Date : 2024-01-01DOI: 10.2174/0115665232261931231006103234
Ammara Saleem, Maira Javed, Muhammad Furqan Akhtar, Ali Sharif, Bushra Akhtar, Muhammad Naveed, Uzma Saleem, Mirza Muhammad Faran Ashraf Baig, Hafiz Muhammad Zubair, Talha Bin Emran, Mohammad Saleem, Ghulam Md Ashraf
{"title":"Current Updates on the Role of MicroRNA in the Diagnosis and Treatment of Neurodegenerative Diseases.","authors":"Ammara Saleem, Maira Javed, Muhammad Furqan Akhtar, Ali Sharif, Bushra Akhtar, Muhammad Naveed, Uzma Saleem, Mirza Muhammad Faran Ashraf Baig, Hafiz Muhammad Zubair, Talha Bin Emran, Mohammad Saleem, Ghulam Md Ashraf","doi":"10.2174/0115665232261931231006103234","DOIUrl":"10.2174/0115665232261931231006103234","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs (miRNA) are small noncoding RNAs that play a significant role in the regulation of gene expression. The literature has explored the key involvement of miRNAs in the diagnosis, prognosis, and treatment of various neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). The miRNA regulates various signalling pathways; its dysregulation is involved in the pathogenesis of NDD.</p><p><strong>Objective: </strong>The present review is focused on the involvement of miRNAs in the pathogenesis of NDD and their role in the treatment or management of NDD. The literature provides comprehensive and cutting-edge knowledge for students studying neurology, researchers, clinical psychologists, practitioners, pathologists, and drug development agencies to comprehend the role of miRNAs in the NDD's pathogenesis, regulation of various genes/signalling pathways, such as α-synuclein, P53, amyloid-β, high mobility group protein (HMGB1), and IL-1β, NMDA receptor signalling, cholinergic signalling, etc. Methods: The issues associated with using anti-miRNA therapy are also summarized in this review. The data for this literature were extracted and summarized using various search engines, such as Google Scholar, Pubmed, Scopus, and NCBI using different terms, such as NDD, PD, AD, HD, nanoformulations of mRNA, and role of miRNA in diagnosis and treatment.</p><p><strong>Results: </strong>The miRNAs control various biological actions, such as neuronal differentiation, synaptic plasticity, cytoprotection, neuroinflammation, oxidative stress, apoptosis and chaperone-mediated autophagy, and neurite growth in the central nervous system and diagnosis. Various miRNAs are involved in the regulation of protein aggregation in PD and modulating β-secretase activity in AD. In HD, mutation in the huntingtin (Htt) protein interferes with Ago1 and Ago2, thus affecting the miRNA biogenesis. Currently, many anti-sense technologies are in the research phase for either inhibiting or promoting the activity of miRNA.</p><p><strong>Conclusion: </strong>This review provides new therapeutic approaches and novel biomarkers for the diagnosis and prognosis of NDDs by using miRNA.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"122-134"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49675258","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 Oral Bio-banks Past, Present and Future; Challenges and Opportunities.","authors":"Gangadhar Baniekal Hiremath, Kondragunta Omkarbabu, Madhavi Hemant Kokate, Baskar Venkidasamy, Murugesan Krishnan, Arun Murugaiyan","doi":"10.2174/1566523223666230801090355","DOIUrl":"10.2174/1566523223666230801090355","url":null,"abstract":"<p><p>Biobank involves collecting, processing, storing, and organizing biosamples, along with relevant personal and health information such as medical history, family records, genetics data, and lifestyle details, for medical research and clinical care. Oral biobanking is a recently evolved field alongside the rising of precision medicine due to recent research findings in oral oncology and other oral complaints, namely caries and periodontal disease. The common samples in oral biobanks are matured and primary teeth, dental pulp cells, oral biopsies, oral rinses, saliva, and swabs from the buccal region. Moreover, biobank should not conceive of as a static collection of samples and data but as a dynamic resource for developing novel techniques that meet current scientific demands through international networking. However, the major bottlenecks associated with oral biobanks are privacy, processing of samples, normalization of data, extended durability of interest markers of banked samples, and financial sustainability of biobanks. Thus in this correspondence, we argue that an alternative approach is urgently needed to protect the interests of many stakeholders.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"2-3"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9966088","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}
Boyi Ma, Dai-Jun Zhang, Yabin Hu, Xianghan Chen, Ruining Gong, Ke Lei, Qian Yu, He Ren
{"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}
Current gene therapyPub Date : 2024-01-01DOI: 10.2174/0115665232262167231012102837
Shikha Yadav, Javed Khan, Agrima Yadav
{"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}