Pub Date : 2026-03-09DOI: 10.1016/j.ymthe.2026.02.027
Mario Escobar,Saad A Malik,Mira A Srinivasa,Miguel A Mendez-Sosa,Jessica M Miller,Samantha L Lydon,Sandy N Luong,Pretty R Mathew,Riham R E Abouleisa,Suridh Chakravarty,Saliha Pathan,Tamer M A Mohamed,Ravi K Ghanta,Isaac B Hilton
Insufficient energy supply due to impaired mitochondria has emerged as a key pathological factor in the development of heart failure (HF) after myocardial infarction (MI). Unfortunately, no current therapeutic strategies directly augment myocardial energy production. While mitochondrial biogenesis is orchestrated by the activity of multiple genes, activation of PPARGC1A, a key regulator, can increase cellular mitochondria; however, supraphysiological levels of PPARGC1A result in adverse tissue remodeling and heart dysfunction. CRISPR activation (CRISPRa) technologies present a unique opportunity to address these shortcomings, as they enable tunable control over endogenous target gene expression. Here, we demonstrate that transcriptional activation of PPARGC1A using CRISPRa increases cellular mitochondria in human cell types. This effect is mediated through the activation of transcriptional programs driving mitochondrial biogenesis, mitochondrial function, and cellular bioenergetics. These activated transcriptional programs synergize to increase ATP production and reserve capacity in human cardiomyocytes. CRISPRa targeting of PPARGC1A in vivo increases cardiac mitochondria to recover heart ejection fraction in an acute MI model. Furthermore, CRISPRa acts on the adult human heart to increase PPARGC1A protein and cellular mitochondria, elevating mitochondrial function in both normal and HF-diagnosed hearts. These results provide the first proof of concept that endogenous gene activation via CRISPRa can improve heart function after MI.
{"title":"CRISPR-Cas-based activation of PPARGC1A boosts endogenous mitochondria and enhances cardiac function after myocardial infarction.","authors":"Mario Escobar,Saad A Malik,Mira A Srinivasa,Miguel A Mendez-Sosa,Jessica M Miller,Samantha L Lydon,Sandy N Luong,Pretty R Mathew,Riham R E Abouleisa,Suridh Chakravarty,Saliha Pathan,Tamer M A Mohamed,Ravi K Ghanta,Isaac B Hilton","doi":"10.1016/j.ymthe.2026.02.027","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.02.027","url":null,"abstract":"Insufficient energy supply due to impaired mitochondria has emerged as a key pathological factor in the development of heart failure (HF) after myocardial infarction (MI). Unfortunately, no current therapeutic strategies directly augment myocardial energy production. While mitochondrial biogenesis is orchestrated by the activity of multiple genes, activation of PPARGC1A, a key regulator, can increase cellular mitochondria; however, supraphysiological levels of PPARGC1A result in adverse tissue remodeling and heart dysfunction. CRISPR activation (CRISPRa) technologies present a unique opportunity to address these shortcomings, as they enable tunable control over endogenous target gene expression. Here, we demonstrate that transcriptional activation of PPARGC1A using CRISPRa increases cellular mitochondria in human cell types. This effect is mediated through the activation of transcriptional programs driving mitochondrial biogenesis, mitochondrial function, and cellular bioenergetics. These activated transcriptional programs synergize to increase ATP production and reserve capacity in human cardiomyocytes. CRISPRa targeting of PPARGC1A in vivo increases cardiac mitochondria to recover heart ejection fraction in an acute MI model. Furthermore, CRISPRa acts on the adult human heart to increase PPARGC1A protein and cellular mitochondria, elevating mitochondrial function in both normal and HF-diagnosed hearts. These results provide the first proof of concept that endogenous gene activation via CRISPRa can improve heart function after MI.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"14 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-06DOI: 10.1016/j.ymthe.2026.03.002
Iddo Magen, Hannah Marlene Kaneb, Maria Masnata, Nisha Pulimood, Anna Emde, Angela Genge, Eran Hornstein
The activity of the RNase III enzyme DICER is downregulated in both sporadic and genetic forms of amyotrophic lateral sclerosis (ALS). Accordingly, hundreds of microRNAs (miRNAs) are broadly downregulated, leading to de-repression of their mRNA targets. Enoxacin is a fluoroquinolone that enhances DICER activity and miRNA biogenesis. Here, we tested for the first time the molecular effect of enoxacin on miRNA biogenesis in ALS patients and demonstrated that enoxacin's engagement with DICER can be pharmacodynamically monitored via miRNA levels in human subjects. In an investigator-initiated, first-in-human study (REALS1), we explored miRNAs as pharmacodynamic biomarkers of DICER activation. Patients with sporadic ALS received oral enoxacin twice daily for 30 days in a double-blind, randomized clinical trial. The study demonstrated comparable enoxacin levels in plasma and cerebrospinal fluid (CSF). Furthermore, an increase in cell-free miRNA levels in both plasma and CSF at all time points following enoxacin treatment (400 or 800 mg/day), was measured relative to baseline. Additionally, no serious adverse events were reported. In conclusion, pharmacological enhancement of DICER activity by enoxacin increases miRNA biogenesis in patients with ALS. These results support further investigation of enoxacin efficacy in larger clinical trials.
{"title":"Cell-free miRNAs are pharmacodynamic biomarkers for enhanced DICER activity by enoxacin in human patients with ALS.","authors":"Iddo Magen, Hannah Marlene Kaneb, Maria Masnata, Nisha Pulimood, Anna Emde, Angela Genge, Eran Hornstein","doi":"10.1016/j.ymthe.2026.03.002","DOIUrl":"10.1016/j.ymthe.2026.03.002","url":null,"abstract":"<p><p>The activity of the RNase III enzyme DICER is downregulated in both sporadic and genetic forms of amyotrophic lateral sclerosis (ALS). Accordingly, hundreds of microRNAs (miRNAs) are broadly downregulated, leading to de-repression of their mRNA targets. Enoxacin is a fluoroquinolone that enhances DICER activity and miRNA biogenesis. Here, we tested for the first time the molecular effect of enoxacin on miRNA biogenesis in ALS patients and demonstrated that enoxacin's engagement with DICER can be pharmacodynamically monitored via miRNA levels in human subjects. In an investigator-initiated, first-in-human study (REALS1), we explored miRNAs as pharmacodynamic biomarkers of DICER activation. Patients with sporadic ALS received oral enoxacin twice daily for 30 days in a double-blind, randomized clinical trial. The study demonstrated comparable enoxacin levels in plasma and cerebrospinal fluid (CSF). Furthermore, an increase in cell-free miRNA levels in both plasma and CSF at all time points following enoxacin treatment (400 or 800 mg/day), was measured relative to baseline. Additionally, no serious adverse events were reported. In conclusion, pharmacological enhancement of DICER activity by enoxacin increases miRNA biogenesis in patients with ALS. These results support further investigation of enoxacin efficacy in larger clinical trials.</p>","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-06DOI: 10.1016/j.ymthe.2026.03.003
Yangeng Wang,Xie Liu,Wenzhe Xuan,Wanling Huang,Yueqiang Zhu,Chengqiong Mao,Yang Liu
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease with limited therapeutic options. The STING signaling pathway, particularly in alveolar macrophages (AMs), has been identified as a critical driver of fibrosis. However, achieving efficient and selective drug delivery to these pathogenic macrophages in the distal lung represents the major hurdle that hinders its clinical translation. To overcome this, we employed a systematic orthogonal screening strategy to develop a macrophage-targeted lipid nanoparticle (LNP) platform. Our optimized formulation, mCas9/gSting@DOPS, demonstrated over 7-fold greater macrophage expression efficiency compared to commercial formulations and was engineered for precise in vivo Sting1 gene editing. This system leverages surface phosphatidylserine (PS) for selective uptake and encapsulates a CRISPR/Cas9 mRNA payload. Following inhalation, LNPs selectively accumulated in target macrophages within a murine model of pulmonary fibrosis. This targeted delivery resulted in effective Sting1 gene disruption, suppression of downstream STING signaling, and reduced secretion of pro-fibrotic cytokines. Functionally, treatment with mCas9/gSting@DOPS LNPs significantly attenuated collagen deposition, alleviated alveolar collapse, and remodeled the fibrotic immune microenvironment. Notably, this therapeutic approach prolonged survival without evidence of systemic toxicity. Our findings establish that our orthogonally-optimized LNP platform enables potent and clinically viable molecular therapy for IPF by efficiently targeting pulmonary macrophages.
{"title":"Inhalable Lipid Nanoparticles for Macrophage-Specific STING Gene Editing to Ameliorate Pulmonary Fibrosis.","authors":"Yangeng Wang,Xie Liu,Wenzhe Xuan,Wanling Huang,Yueqiang Zhu,Chengqiong Mao,Yang Liu","doi":"10.1016/j.ymthe.2026.03.003","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.03.003","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease with limited therapeutic options. The STING signaling pathway, particularly in alveolar macrophages (AMs), has been identified as a critical driver of fibrosis. However, achieving efficient and selective drug delivery to these pathogenic macrophages in the distal lung represents the major hurdle that hinders its clinical translation. To overcome this, we employed a systematic orthogonal screening strategy to develop a macrophage-targeted lipid nanoparticle (LNP) platform. Our optimized formulation, mCas9/gSting@DOPS, demonstrated over 7-fold greater macrophage expression efficiency compared to commercial formulations and was engineered for precise in vivo Sting1 gene editing. This system leverages surface phosphatidylserine (PS) for selective uptake and encapsulates a CRISPR/Cas9 mRNA payload. Following inhalation, LNPs selectively accumulated in target macrophages within a murine model of pulmonary fibrosis. This targeted delivery resulted in effective Sting1 gene disruption, suppression of downstream STING signaling, and reduced secretion of pro-fibrotic cytokines. Functionally, treatment with mCas9/gSting@DOPS LNPs significantly attenuated collagen deposition, alleviated alveolar collapse, and remodeled the fibrotic immune microenvironment. Notably, this therapeutic approach prolonged survival without evidence of systemic toxicity. Our findings establish that our orthogonally-optimized LNP platform enables potent and clinically viable molecular therapy for IPF by efficiently targeting pulmonary macrophages.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"30 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147371010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-06DOI: 10.1016/j.ymthe.2026.02.037
Bin Pan,Robert Peter Gale,Zhiling Yan
{"title":"Cross-species insights: Optimizing chimeric antigen receptor T cell therapy in humans with insights from dogs.","authors":"Bin Pan,Robert Peter Gale,Zhiling Yan","doi":"10.1016/j.ymthe.2026.02.037","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.02.037","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"199 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147371012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.1016/j.ymthe.2026.03.005
Eun Ji Shin,Yuri Choi,Eun Je Jeon,Kang-In Lee,Kyu-Jun Lee,Young Ju Son,Min Ji Son,Seokjoong Kim,Seung-Woo Cho,Jae Young Lee
Chronic limb-threatening ischemia (CLTI) is a severe vascular disorder characterized by tissue hypoxia and oxidative stress that limit the efficacy of regenerative therapies. Mesenchymal stem/stromal cells (MSCs) hold promise for CLTI treatment through paracrine angiogenic and immunomodulatory signaling, yet their survival and function are compromised in the reactive oxygen species-rich ischemic microenvironment. Here, we utilized CRISPR/Cas9 to generate a targeted knockout of Kelch-like ECH-associated protein 1 (KEAP1), the negative regulator of the antioxidant transcription factor NRF2, in human bone marrow-derived MSCs. KEAP1 editing activated the NRF2 pathway, reduced intracellular oxidative stress, and reprogrammed redox and paracrine gene networks. Edited MSCs exhibited enhanced viability, sustained secretion of proangiogenic cytokines, and improved tissue perfusion and arteriogenesis in a murine model of CLTI. These findings establish KEAP1 gene editing as a permanent, integration-free strategy to augment MSC resistance and therapeutic efficacy in oxidative ischemic environments.
{"title":"Targeted KEAP1 Disruption Enhances Antioxidant Defense And Mesenchymal Stromal Cell Therapy For Chronic Limb-threatening Ischemia.","authors":"Eun Ji Shin,Yuri Choi,Eun Je Jeon,Kang-In Lee,Kyu-Jun Lee,Young Ju Son,Min Ji Son,Seokjoong Kim,Seung-Woo Cho,Jae Young Lee","doi":"10.1016/j.ymthe.2026.03.005","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.03.005","url":null,"abstract":"Chronic limb-threatening ischemia (CLTI) is a severe vascular disorder characterized by tissue hypoxia and oxidative stress that limit the efficacy of regenerative therapies. Mesenchymal stem/stromal cells (MSCs) hold promise for CLTI treatment through paracrine angiogenic and immunomodulatory signaling, yet their survival and function are compromised in the reactive oxygen species-rich ischemic microenvironment. Here, we utilized CRISPR/Cas9 to generate a targeted knockout of Kelch-like ECH-associated protein 1 (KEAP1), the negative regulator of the antioxidant transcription factor NRF2, in human bone marrow-derived MSCs. KEAP1 editing activated the NRF2 pathway, reduced intracellular oxidative stress, and reprogrammed redox and paracrine gene networks. Edited MSCs exhibited enhanced viability, sustained secretion of proangiogenic cytokines, and improved tissue perfusion and arteriogenesis in a murine model of CLTI. These findings establish KEAP1 gene editing as a permanent, integration-free strategy to augment MSC resistance and therapeutic efficacy in oxidative ischemic environments.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"6 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with inflammatory bowel disease (IBD) exhibit a dysregulated bile acid pool, characterized by increased primary and decreased secondary bile acids, largely due to gut microbiota dysfunction. However, the impact of colitis on hepatic bile acid synthesis remains poorly understood. In this study, analyses of public datasets, in-house patient samples, and an animal model revealed that colitis enhances flux through the classical bile acid synthesis pathway while suppressing the alternative pathway. Oral administration of chenodeoxycholic acid (CDCA) redirected bile acid synthesis toward the alternative pathway and alleviated colitis in mice. Single-cell RNA sequencing and adoptive transfer experiments demonstrated that CDCA administration reduced pro-inflammatory neutrophil accumulation in the colon by downregulating epithelial-derived CXCL2, a finding validated by in vitro assays and a transgenic mouse model. Mechanistic studies further demonstrated that lithocholic acid (LCA), a CDCA metabolite in the gut, activates colonic epithelial VDR, thereby suppressing CXCL2 via NFκB inhibition. Clinical sample analyses supported these findings, showing that a higher cholic acid (CA) to CDCA ratio positively correlates with neutrophil counts and CXCL2 levels in IBD patients. Together, these findings suggest a critical role of hepatic bile acid synthesis pathways in IBD pathogenesis and highlight CDCA as a potential therapeutic candidate.
{"title":"Chenodeoxycholic acid administration redirects the bile acid synthetic pathway to limit pro-inflammatory neutrophil infiltration and alleviate colitis.","authors":"Wei Zhang,Xinkai Wu,Ye Feng,Luxi Yin,Jiansheng Xie,Rongjie Zhao,Guimei Wang,Bingru Lin,Zhipeng Fang,Eryun Zhang,Hongming Pan,Wendong Huang,Weidong Han","doi":"10.1016/j.ymthe.2026.03.004","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.03.004","url":null,"abstract":"Patients with inflammatory bowel disease (IBD) exhibit a dysregulated bile acid pool, characterized by increased primary and decreased secondary bile acids, largely due to gut microbiota dysfunction. However, the impact of colitis on hepatic bile acid synthesis remains poorly understood. In this study, analyses of public datasets, in-house patient samples, and an animal model revealed that colitis enhances flux through the classical bile acid synthesis pathway while suppressing the alternative pathway. Oral administration of chenodeoxycholic acid (CDCA) redirected bile acid synthesis toward the alternative pathway and alleviated colitis in mice. Single-cell RNA sequencing and adoptive transfer experiments demonstrated that CDCA administration reduced pro-inflammatory neutrophil accumulation in the colon by downregulating epithelial-derived CXCL2, a finding validated by in vitro assays and a transgenic mouse model. Mechanistic studies further demonstrated that lithocholic acid (LCA), a CDCA metabolite in the gut, activates colonic epithelial VDR, thereby suppressing CXCL2 via NFκB inhibition. Clinical sample analyses supported these findings, showing that a higher cholic acid (CA) to CDCA ratio positively correlates with neutrophil counts and CXCL2 levels in IBD patients. Together, these findings suggest a critical role of hepatic bile acid synthesis pathways in IBD pathogenesis and highlight CDCA as a potential therapeutic candidate.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"110 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.1016/j.ymthe.2026.03.006
Karrie M Kiang,Yixiong Shen,Yogesh K H Wong,Bo Chen,Junbo Liao,Anza Mnahal,Wanjun Tang,Zhiyuan Zhu,Shuhan Cao,Carmen S C Lo,Sang Jin Lee,Hongbo Guo,Liyang Zhang,Gilberto Ka-Kit Leung
Tumor cells adapt to therapeutic stress by preserving mitochondrial integrity through mitophagy, but excessive mitophagy can overwhelm this adaptative mechanism and precipitate mitochondrial collapse. Here, we demonstrate that 1,25-dihydroxyvitamin D3 (1,25D3) reduces glioblastoma resistance to the standard chemotherapeutics temozolomide by driving mitophagic overload and mitochondrial dysfunction. We identified mitochondrial sirtuin SIRT4 as a key downstream effector of mitochondrial metabolism and quality control triggered by 1,25D3-induced mitochondrial stress. Pharmacological levels of 1,25D3 activate mitophagy by transcriptionally upregulating SIRT4 through vitamin D receptor (VDR) signaling. SIRT4, which is frequently downregulated in glioblastoma, suppresses glioblastoma glutamine metabolism by inhibiting glutamate dehydrogenase activity and limiting α-ketoglutarate availability, thereby integrating metabolic stress with enhanced mitophagy. This VDR-SIRT4 axis shifts mitophagy from a cytoprotective process to a lethal pathway, selectively sensitizing tumor cells while sparing normal astrocytes and brain tissue. By exploiting mitochondrial quality control as a metabolic vulnerability, 1,25D3 enhances chemotherapeutic efficacy and provides a translational rationale for repurposing 1,25D3 in resistant glioblastoma.
{"title":"1,25D3 reprograms mitochondrial quality control via sirtuin and sensitizes glioblastoma to chemotherapy.","authors":"Karrie M Kiang,Yixiong Shen,Yogesh K H Wong,Bo Chen,Junbo Liao,Anza Mnahal,Wanjun Tang,Zhiyuan Zhu,Shuhan Cao,Carmen S C Lo,Sang Jin Lee,Hongbo Guo,Liyang Zhang,Gilberto Ka-Kit Leung","doi":"10.1016/j.ymthe.2026.03.006","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.03.006","url":null,"abstract":"Tumor cells adapt to therapeutic stress by preserving mitochondrial integrity through mitophagy, but excessive mitophagy can overwhelm this adaptative mechanism and precipitate mitochondrial collapse. Here, we demonstrate that 1,25-dihydroxyvitamin D3 (1,25D3) reduces glioblastoma resistance to the standard chemotherapeutics temozolomide by driving mitophagic overload and mitochondrial dysfunction. We identified mitochondrial sirtuin SIRT4 as a key downstream effector of mitochondrial metabolism and quality control triggered by 1,25D3-induced mitochondrial stress. Pharmacological levels of 1,25D3 activate mitophagy by transcriptionally upregulating SIRT4 through vitamin D receptor (VDR) signaling. SIRT4, which is frequently downregulated in glioblastoma, suppresses glioblastoma glutamine metabolism by inhibiting glutamate dehydrogenase activity and limiting α-ketoglutarate availability, thereby integrating metabolic stress with enhanced mitophagy. This VDR-SIRT4 axis shifts mitophagy from a cytoprotective process to a lethal pathway, selectively sensitizing tumor cells while sparing normal astrocytes and brain tissue. By exploiting mitochondrial quality control as a metabolic vulnerability, 1,25D3 enhances chemotherapeutic efficacy and provides a translational rationale for repurposing 1,25D3 in resistant glioblastoma.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"8 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-04Epub Date: 2026-02-20DOI: 10.1016/j.ymthe.2026.02.023
Andrew D Brim, Leonardo M R Ferreira
{"title":"From blind to bound: CRISPR restores IL-2 responsiveness in patient Tregs.","authors":"Andrew D Brim, Leonardo M R Ferreira","doi":"10.1016/j.ymthe.2026.02.023","DOIUrl":"10.1016/j.ymthe.2026.02.023","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"1301-1303"},"PeriodicalIF":12.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12974190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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