Current drug metabolism最新文献

{"title":"Comparative Proteomics of Hepatocytes And Hepatic Cell Lines Using Swath-MS Reveals Significant Variations In Proteins Involved In Energy, Lipid, And Xenobiotic Metabolism.","authors":"Anitha Saravanakumar, Rohitash Jamwal, Benjamin B Barlock, Xin Bush, Fatemeh Akhlaghi","doi":"10.2174/0113892002403596251122091342","DOIUrl":"10.2174/0113892002403596251122091342","url":null,"abstract":"<p><strong>Introduction: </strong>Human hepatic carcinoma cell lines are widely used in vitro to study lipid and xenobiotic metabolism, as well as glucose regulation in both normal and diseased states. However, their validity is often questioned due to variability in protein expression compared to primary human hepatocytes (cHH). This study aimed to quantify protein abundance in various hepatic cell lines versus cHH and human liver tissue homogenate (HLT) using a data-independent acquisition-based total protein approach (DIA-TPA). We compared the global proteome from the whole cell homogenates of HepaRG, HepG2, and Huh7 cell lines with that of cHH and HLT.</p><p><strong>Methods: </strong>Proteins in whole cell homogenates were digested in solution using pressure-cycling technology (PCT). DIA was performed via sequential window acquisition of theoretical mass spectra (SWATH-MS), and MS2 spectra were quantified using Spectronaut™, followed by analysis with TPA.</p><p><strong>Results: </strong>We identified 2715, 2578, 2874, 2717, and 3083 proteins in HepaRG, HepG2, Huh7, cHH, and HLT, respectively, at a 1% FDR. The global proteome of cHH significantly differed from that of the cancer hepatic cell lines. Among the cell lines, the global and ADME protein profile of HepaRG most closely correlated with cHH, with 89 out of 101 ADME proteins identified. Clinically relevant DMEs from the CYP450 family (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and the UGT family (UGT1A1, UGT1A3, UGT1A6, UGT2B7, and UGT2B15) were quantifiable in human hepatocytes, human liver tissue, and the HepaRG cell line. The Huh7 cell line exhibited a higher abundance of proteins related to gluconeogenesis and glycolysis compared to other groups.</p><p><strong>Conclusion: </strong>This study highlights the potential of untargeted global proteomics in detecting differences in protein expression among various hepatic cell lines and provides a comprehensive database to inform the choice of the cell line in future studies.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"45-57"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050519","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":"Computational Chemistry Approach in the Assessment of Potential Acyl Glucuronide-mediated Toxicity.","authors":"Nathan D Ricke, Markus Walles, Russell Jones, John Davis, Mithat Gunduz","doi":"10.2174/0113892002401464251121074008","DOIUrl":"10.2174/0113892002401464251121074008","url":null,"abstract":"<p><strong>Introduction: </strong>Acyl glucuronides are common phase II metabolites of xenobiotics and can sometimes contribute to idiosyncratic toxicities. Their reactivity is primarily mediated through acyl migration and/or nucleophilic displacement, and shorter acyl glucuronide halflives are associated with increased reactivity. This reactivity can lead to metabolite-induced toxicity, posing a significant risk during drug development.</p><p><strong>Methods: </strong>We developed regression models trained on features derived from Density Functional Theory (DFT) calculations to predict the half-lives of acyl glucuronide metabolites. The aim was to provide a computational tool to guide the design of drug candidates with more stable acyl glucuronide metabolites.</p><p><strong>Results: </strong>The best-performing model achieved a strong correlation between predicted and experimental half-lives, with an R² of 0.67 on the test set. Predicted half-lives for drugs classified as clinically safe were longer than those for drugs in the warning and withdrawn categories, demonstrating a separation comparable to experimentally measured half-lives.</p><p><strong>Discussion: </strong>The model is sufficiently accurate to support the optimization of acyl glucuronides for longer half-lives. Further analysis indicated that acyl glucuronide stability can be modulated by electron-donating and electron-withdrawing groups, effects that are effectively captured by the model.</p><p><strong>Conclusion: </strong>This modeling approach can be applied during drug discovery to reduce the risk of metabolite-related toxicity by enabling in silico screening of compound modifications and ranking them based on predicted effects on acyl glucuronide half-life.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"139-152"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050500","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 Multifaceted Role of Cytochrome P450 Isoenzymes in Alcoholic and Metabolic (Dysfunction) Fatty Liver Diseases.","authors":"Nidal A Qinna, Ola N Estatieh, Bayan Y Ghanim","doi":"10.2174/0113892002422091251125072745","DOIUrl":"10.2174/0113892002422091251125072745","url":null,"abstract":"<p><p>The current review explores the alterations in cytochrome P450 (CYP) activity and expression during alcoholic liver disease (ALD) and metabolic (dysfunction)-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD). CYP is a major family of enzymes involved in the metabolism of numerous endogenous and exogenous compounds. Thus, any change in CYP activity or expression could disrupt metabolic pathways. Alterations in hepatic CYP have been shown to contribute to the development of ALD and MAFLD, and vice versa. CYP isoforms also participate in fatty acid metabolism and are involved in fatty liver development in ALD and MAFLD by regulating various cell signaling pathways and transcription factors. Several mechanisms by which CYP causes oxidative stress and liver injury are reviewed here. Additionally, CYP isoforms are known to break down cholesterol into bile acids, which play a role in lipid absorption in the small intestine and modulate the bile acid pool. This review discusses the role of CYP isoforms in the progression of ALD and MAFLD, as understanding these mechanisms can help identify potential targets for the prevention and treatment of both diseases.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"1-14"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050517","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":"A Systematic Review of Pharmacokinetic Models of Vancomycin in Adult Patients (2020-2024): Trends, Variability, and Key Covariates.","authors":"Raquel Fresquet-Molina, María de Los Ángeles Allende-Bandres, Mercedes Arenere-Mendoza, Lucía Sopena-Carrera, Irene Navarro-Pardo, Ángela Jimeno-Martin, Tránsito Salvador-Gomez, Manuel Gomez-Barrera, Loreto Sáez-Benito-Suescun, Nuria Berenguer-Torrijo","doi":"10.2174/0113892002395979251015105103","DOIUrl":"10.2174/0113892002395979251015105103","url":null,"abstract":"<p><strong>Introduction: </strong>This systematic review aimed to identify, evaluate, and critically an-alyze pharmacokinetic models of vancomycin in adult populations published in PubMed and EMBASE between 2020 and 2024.</p><p><strong>Materials and methods: </strong>Twenty-two studies were included, describing 24 models character-ized by substantial heterogeneity in terms of study populations, methodological design, and covariate selection. Most models were developed in Asia and focused on hospitalized patients, particularly those in intensive care units (ICUs). Data from 2150 patients were analyzed, with an average of 93 patients per model.</p><p><strong>Results: </strong>The models demonstrated high variability in pharmacokinetic parameters, such as vancomycin clearance (Cl) and volume of distribution (Vd), influenced by factors, such as renal function, weight, age, and comorbidities. The meta-analysis conducted on clearance and interindividual variability in clearance (IIV Cl) revealed high heterogeneity among the ana-lyzed studies. The average vancomycin clearance was 4.23 L/h, with higher values observed in neurosurgical, oncohematologic patients, and those with increased renal function. The vol-ume of distribution showed greater variability in obese patients and those undergoing continu-ous renal replacement therapy. Creatinine clearance (ClCr) was identified as a significant co-variate in 66% of the models, while weight was significant in 33%. Other important covariates included age, sex, serum creatinine, serum urea, and the hospital admission unit. The meta-analysis of Cl and IIV Cl showed high heterogeneity among the studies, with I² values of 0.83 for Cl and 0.98 for IIV Cl, indicating substantial variability.</p><p><strong>Discussion: </strong>The limitations of this study included the diversity of the analyzed populations, which made it challenging to assess the model's suitability. While the models showed advances in precision, challenges, such as the lack of external validation and discrepancies in dosing recommendations, remain.</p><p><strong>Conclusion: </strong>This review paper has highlighted the need to validate models in diverse popula-tions and clinical settings to optimize personalized vancomycin therapy in adults. The findings have highlighted the importance of validating or adapting pharmacokinetic models to the spe-cific characteristics of each hospital population.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13223505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548666","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}

{"title":"Molecular Pathways Involved in Drug-Induced Hepatotoxicity: A Mini Review.","authors":"Annu Bhati, Avijit Mazumder, Priyanka Bansal, Salahuddin","doi":"10.2174/0113892002416903251006113913","DOIUrl":"https://doi.org/10.2174/0113892002416903251006113913","url":null,"abstract":"<p><p>Drug-induced hepatotoxicity (DIH) poses a significant clinical challenge due to its unpredicta-ble nature and diverse manifestations. The liver, with its central role in metabolism and close association with the gastrointestinal tract, is particularly susceptible to drug-induced toxicity. DIH encompasses a spectrum of liver injuries, including hepatocellular, cholestatic, and mixed patterns, which may increase the risk of other liver diseases. This review examines diverse examples and molecular mechanisms under-lying DIH, highlighting the influence of genetic predisposition, drug interactions, and pre-existing liver conditions. Given the complexity and variability of hepatotoxic responses to numerous medications, un-derstanding these mechanisms is crucial for improving the diagnosis and management of DIH.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523049","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":"Lung-Targeting Cepharanthine Polymer Micelles Modified with Mannose: Effectiveness Against Acute Lung Injury Evaluated Using in vitro and in vivo Analyses.","authors":"Rui Xue, Yi-Ying Chen, Jia-Hua Mei, Pei-Pei Zhang, Wen-Bin Jin, Li-Li Cui, Xiao-Yu Zhao, Hai-Liang Zhang, Li-Qin Luo, Yun-Shu Ma","doi":"10.2174/0113892002413042251015104239","DOIUrl":"https://doi.org/10.2174/0113892002413042251015104239","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;p&gt;Introduction: The currently available therapies for acute lung injury (ALI), including gluco-corticoids, protease inhibitors, and heparin, have limited clinical efficacy and are often associated with significant side effects. Cepharanthine (CEP) has demonstrated effectiveness in treating pulmonary dis-eases, but its clinical application is restricted by low solubility and poor bioavailability. This study aimed to develop mannosylated cepharanthine-loaded polymeric micelles (MA-CEP-PMs) to improve CEP bio-availability and enhance lung-targeted delivery for the treatment of ALI. &lt;/p&gt;&lt;p&gt; Methods: The pharmacokinetics of MA-CEP-PMs in rats were assessed using Ultra-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS). Lung-targeting ability was evaluated through tissue distribution studies and near-infrared imaging. In a rat model of ALI induced by lipopolysaccharide (LPS), anti-ALI effects were assessed via general physiological indicators, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blot analysis. Hematoxylin-eosin (HE) staining was used to examine hepatotoxicity and nephrotoxicity of MA-CEP-PMs in normal rats. Cyto-toxicity of the mannosylated polyethylene glycol-poly(lactic-co-glycolic acid) copolymer (MA-PEG-PLGA) on NR8383 cells was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Cellular uptake experiments were performed to determine the targeting ability of MA-PEG-PLGA in NR8383 cells, and the effects of MA-CEP-PMs on inflammatory cytokines were analyzed using ELISA.&lt;/p&gt;&lt;p&gt; Results: MA-CEP-PMs significantly increased the AUC and exhibited better lung targeting ability com-pared to the unmodified micelles (P &lt; 0.01). In the ALI model, MA-CEP-PMs improved the thymus and spleen indices, decreased the lung wet-to-dry weight ratio (P &lt; 0.05), alleviated model animal damage, and inhibited inflammatory factor and nuclear factor-κB (NF-κB)-related protein levels (P &lt; 0.05). MA-CEP-PMs exhibited no significant hepatotoxicity or nephrotoxicity. MA-PEG-PLGA exhibited low tox-icity against NR8383 cells and greater cell uptake, indicating stronger targeting of the lung. MA-CEP-PMs also exhibited more potent anti-inflammatory effects.&lt;/p&gt;&lt;p&gt; Discussion: This study focused on the short-term therapeutic effects of ALI, whereas the clinical man-agement of lung injury often requires long-term intervention. Future research should therefore assess the long-term efficacy of this delivery system in chronic lung injury, along with determining its safety profile and potential impacts on extra-pulmonary organs. While the involvement of the NF-κB pathway in the anti-inflammatory effects has been confirmed, it remains to be deciphered whether mannose modification synergistically regulates other signaling pathways and what the specific intracellular targets of CEP are, which would require further exploration through detailed molecular biology experiments.&lt;/p&gt;&lt;p&gt; Conclusion: The MA-CEP-PMs significantly ","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495014","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 Proteomics, Glycomics, and Metabolomics Analyses in Systemic Lupus Erythematosus.","authors":"Rui Xu, Guosong Zhang, Shifang Wang, Tao Yang, Canjian Wang","doi":"10.2174/0113892002430185251015075018","DOIUrl":"https://doi.org/10.2174/0113892002430185251015075018","url":null,"abstract":"<p><p>Systemic Lupus Erythematosus (SLE) is a multifactorial autoimmune disorder in-fluenced by genetic predisposition, immune dysregulation, environmental triggers, and epi-genetic modifications. Despite advances in treatment, many patients experience recurrent symptoms and adverse effects. Recent large-scale studies have revealed significant alterations in proteins, glycopeptides, and metabolites in SLE, deepening our understanding of its path-ogenesis. Emerging omics technologies, such as proteomics, glycomics, and metabolomics, enable the high-throughput identification of disease-related biomarkers. However, biological processes are typically driven by the interplay among multiple molecular layers. Therefore, integrative multi-omics approaches have become essential for uncovering potential bi-omarkers and risk factors. This review summarizes the classification of SLE biomarkers and recent advances in diagnostic applications across proteomics, glycomics, and metabolomics, aiming to support the development of more precise diagnostic strategies for SLE.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451213","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":"Study on the Mechanism of Anti-Cerebral Ischemia-Reperfusion Injury of Ai Pian Based on Network Pharmacology and Metabolomics.","authors":"Jianing Lian, Yilun Ma, Dazhong Lu, Peiru Wang, Mengmeng Zhang, Taiwei Dong","doi":"10.2174/0113892002403752251015105027","DOIUrl":"10.2174/0113892002403752251015105027","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to investigate the mechanism of anti-cerebral ischemia-reperfusion injury (anti-CIRI) of Ai pian by using the network pharmacology approach combined with serum metabolomics technique based on UPLC-MS.</p><p><strong>Methods: </strong>The cerebral ischemia-reperfusion injury (CIRI) model was established by middle cerebral artery occlusion (MCAO). The therapeutic effect of Ai pian on CIRI rats was evaluated by behavioral test, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl staining, and hematoxylin-eosin (HE) staining. The active compound-potential target-disease network for Ai Pian in the treatment of CIRI was established using network pharmacology methods. Rat serum was detected by the metabolomics technique based on UPLC-MS. A Western blot was used to validate common targets of the network pharmacology approach combined with serum metabolomics.</p><p><strong>Results: </strong>The process of treating CIRI with Ai Pian involved regulating enzyme, nuclear receptor, and transcription factor activity, managing the inflammatory response, and participating in biofilm composition. Twenty endogenous potential biomarkers were screened and submitted to MetaboAnalyst 6.0 for pathway and enrichment analysis. Four metabolic pathways were identified: butanoate metabolism, fructose and mannose metabolism, alanine, aspartate, and glutamate metabolism, and pyrimidine metabolism. Fructose and mannose metabolism and pyrimidine metabolism were two key pathways. Western blot analysis suggested that DHODH, TYMS, and AKR1B1 may be targets through which therapeutic effects are exerted.</p><p><strong>Conclusion: </strong>This research contributed to the development of Ai pian as an adjunctive drug for treating CIRI and provided a basis for further research on CIRI.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13223493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430395","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}

{"title":"Comparative in Vitro Metabolic Profile Study of Five Cathinone Derivatives.","authors":"Zexuan Li, Sufang Xiang, Tian Zheng, Guoping Wu, Liang Wu","doi":"10.2174/0113892002348484250309011657","DOIUrl":"https://doi.org/10.2174/0113892002348484250309011657","url":null,"abstract":"<p><strong>Background: </strong>Cathinone derivatives as new psychoactive substances have attracted worldwide attention in recent years. They have strong excitatory effects on the human central nervous system, which is extremely abusive and harmful. As they are easy to be structurally modified, and rapidly metabolized and excreted after taken, clarifying their metabolic profile is of significant importance to provide useful information for their identification or forensic purposes.</p><p><strong>Objective: </strong>In this paper, a comparative in vitro metabolic profile study of five cathinone derivatives (4/3/2- methylmethcathinone and 4/3-methoxymethcathinone) was performed, including their metabolic stability in the simulated gastrointestinal tract, mass spectrometry fragmentation behavior, possible metabolic pathways and metabolites in human liver microsomal incubation system, and revealing the key metabolic enzyme isoforms involving in their biotransformation.</p><p><strong>Methods: </strong>In vitro incubation was performed in simulated gastric/intestinal fluid and human liver microsomes, fragmentation behavior study and metabolite identification were investigated by LC-Q-TOF/MS, and metabolic stability study, along with metabolic enzyme screening were analyzed using LC-MS/MS.</p><p><strong>Results: </strong>Almost all the cathinone derivatives tested were stable in the simulated gastric/intestinal fluid; characteristic fragmentation pathway and diagnostic fragment ions of the cathinone derivatives were analyzed; the key metabolic pathways of 4/3-methylmethcathinone and 4/3-methoxymethcathinone revealed were hydroxylation and demethylation, which were catalyzed by CYP2D6. The methyl-substituted position would significantly affect the metabolic pathway of the methylmethcathinone.</p><p><strong>Conclusion: </strong>This study revealed the mass spectral fragmentation pattern and the in vitro metabolic behavior of the selected cathinone derivatives, providing meaningful information and scientific evidence in predicting their metabolic potential in vivo, and also promoting their analysis, detection, and clinical use.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656378","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":"Transformative CRISPR-Cas9 Technologies: A Review of Molecular Mechanisms, Precision Editing Techniques, and Clinical Progress in Sickle Cell Disease.","authors":"Komal, Prabhjot Kaur, Nidhi Arora, Jyotiram A Sawale, Amandeep Singh","doi":"10.2174/0113892002356293250225094826","DOIUrl":"https://doi.org/10.2174/0113892002356293250225094826","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a hereditary blood disorder resulting from the production of distorted hemoglobin molecules that cause red blood cells to adopt a sickle or crescent-like shape. This disease affects millions of people, particularly those of African, Mediterranean, Middle Eastern, or South Asian descent. In recent years, however, advancements in the CRISPR-Cas9 gene-editing systems have surged. CRISPR stands for clustered regularly interspaced short palindromic repeats, referring to a specific organization of short, partially repeated DNA sequences in prokaryotic genomes. The CRISPR-Cas9 technique is based on the type II CRISPR system of bacteria and involves the Cas9 nuclease, which is targeted to a particular genome section with the help of single-guide RNA. Initially used for random mutations and small sequence alterations, genome editing methods have advanced to achieve large-scale DNA segment manipulation. The BE and PE-- type CRISPR-Cas9 genome editing variants provide new therapeutic options for genetic disorders, improving patients' prognosis. Curative gene editing using CRISPR-Cas9 technology to correct HBB gene mutations that cause SCD represents a revolutionary therapeutic development. These advances bring new hope to patients with previously untreatable diseases, potentially offering a future where genetic disorders can be addressed at their roots. A major objective of CRISPR technology is to enhance its precision and speed, both critical for effective gene editing. This review focuses on molecular mechanisms of CRISPR-Cas9 technology, CRISPR-- Cas9-based approaches for HBB gene modification, clinical trials, patients with sickle cell disease, and advances in CRISPR technology for sickle cell disease.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566373","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}