Molecular Therapy最新文献_第8页

AAV-Sparcl1 Promotes Hair Cell Regeneration by Increasing Supporting Cell Plasticity. AAV-Sparcl1 通过增强支持细胞的可塑性促进毛细胞再生

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 DOI: 10.1016/j.ymthe.2025.03.054

Nianci Li, Fangzhi Tan, Liyan Zhang, Xiaoqiong Ding, Qiuhan Sun, Man Wang, Ziyu Zhang, Yicheng Lu, Yinyi Zhou, Xiaoyun Qian, Fanglei Ye, Jieyu Qi, Renjie Chai

{"title":"AAV-Sparcl1 Promotes Hair Cell Regeneration by Increasing Supporting Cell Plasticity.","authors":"Nianci Li, Fangzhi Tan, Liyan Zhang, Xiaoqiong Ding, Qiuhan Sun, Man Wang, Ziyu Zhang, Yicheng Lu, Yinyi Zhou, Xiaoyun Qian, Fanglei Ye, Jieyu Qi, Renjie Chai","doi":"10.1016/j.ymthe.2025.03.054","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.054","url":null,"abstract":"Sensorineural hearing deficiency caused by hair cell damage represents a prevalent sensory deficit disorder. In mammals, age-related reduction in plasticity of inner ear supporting cells (recognized as hair cell precursors) compromises their trans-differentiation capacity, resulting in impaired spontaneous hair cell regeneration post-injury. Therapeutic reprogramming of supporting cells to functionally replace damaged hair cells has emerged as a promising strategy for sensorineural hearing loss treatment. In this study, we demonstrate that the secretory protein Sparcl1 enhances supporting cell reprogramming and hair cell regeneration in both vitro and vivo models. Through adeno-associated virus (AAV)-mediated overexpression system, we successfully achieved in vivo expansion of inner ear organoids accompanied by hair cell differentiation. RNA-seq analysis revealed that Sparcl1 overexpression stimulates supporting cell proliferation via follistatin (Fst) activation and extracellular matrix (ECM) remodeling. Notably, both AAV-ie-Sparcl1 delivery and recombinant Sparcl1 protein administration effectively induced supporting cell differentiation into hair cells in vivo. Collectively, our findings establish Sparcl1 as a potent positive regulator of hair cell regeneration and elucidate mechanisms by which secretory proteins regulate supporting cell plasticity.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780666","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}

引用次数: 0

Advances in AAV Capsid Engineering: Integrating Rational Design, Directed Evolution and Machine Learning. AAV 胶囊工程的进展：整合合理设计、定向进化和机器学习。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-01 DOI: 10.1016/j.ymthe.2025.03.056

Alan M Nisanov, Julio A Rivera de Jesús, David V Schaffer

引用次数: 0

Ex vivo Modification of Hematopoietic Stem and Progenitor Cells for Gene Therapy.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-01 DOI: 10.1016/j.ymthe.2025.03.058

David A Williams, Donald B Kohn, Adrian J Thrasher

{"title":"Ex vivo Modification of Hematopoietic Stem and Progenitor Cells for Gene Therapy.","authors":"David A Williams, Donald B Kohn, Adrian J Thrasher","doi":"10.1016/j.ymthe.2025.03.058","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.058","url":null,"abstract":"The development of viral vectors has been particularly critical for genetic therapies of hematologic diseases. Prior to the development of retrovirus vectors, gene transfer into mammalian cells was accomplished by transduction of DNA plasmids by chemical means and later by electroporation. The main limitation of these methods is the inefficiency of transfer of intact sequences, and particularly with electroporation significant cell death of the manipulated cells. The earliest successful human gene therapy trials utilized γ-RVV and many of the techniques developed in the 1980s. A breakthrough for the field was the exploitation and development of human immunodeficiency virus for transfer vectors, termed lentivirus vectors. In this review, we highlight uses of retro- and lentivirus vectors in monogenic diseases in which hematopoietic stem cells are used in the autologous setting to treat immunodeficiencies, hemoglobinopathies and metabolic diseases. The three authors' perspective represent experiences in the field over four decades that encompasses both basic translational research and development and oversight of early and ongoing gene therapy trials utilizing viral vectors.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772765","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}

引用次数: 0

Non-relapse mortality with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-31 DOI: 10.1016/j.ymthe.2025.03.048

Tobias Tix, Mohammad Alhomoud, Roni Shouval, Gloria Iacoboni, Edward R Scheffer Cliff, Doris K Hansen, Saad Z Usmani, Gilles Salles, Miguel-Angel Perales, David M Cordas Dos Santos, Kai Rejeski

{"title":"Non-relapse mortality with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma.","authors":"Tobias Tix, Mohammad Alhomoud, Roni Shouval, Gloria Iacoboni, Edward R Scheffer Cliff, Doris K Hansen, Saad Z Usmani, Gilles Salles, Miguel-Angel Perales, David M Cordas Dos Santos, Kai Rejeski","doi":"10.1016/j.ymthe.2025.03.048","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.048","url":null,"abstract":"Bispecific antibodies (BsAb) are associated with distinct immune-related toxicities that impact morbidity and mortality. This systematic review and meta-analysis examined non-relapse mortality (NRM) with BsAb therapy in B-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). A PubMed and Embase search up to October 2024 identified 29 studies (21 NHL, 8 MM) involving 2,535 patients. The overall NRM point estimate was 4.7% (95% CI 3.4-6.4%) with a median follow-up of 12.0 months. We noted no significant difference in NRM across disease entities (NHL: 4.2%, MM: 6.2%, p=0.22). In NHL, prespecified subgroup analyses revealed increased NRM in real-world studies compared to clinical trials. For MM, an association between NRM and higher response rates and longer follow-up was noted. Meta-regression comparing BsAb and CAR-T therapies (n=8,592) showed no significant NRM difference when accounting for key study-level confounders (p=0.96). Overall, infections were the leading cause of NRM, accounting for 71.8% of non-relapse deaths. Of the infection-related deaths, 48% were attributed to COVID-19. In a pre-specified sensitivity analysis excluding COVID-19-fatalities, the overall NRM estimate was 3.5% (95% CI 2.6-4.6%). Taken together, these results provide a benchmark for the estimated NRM with BsAb therapy and highlight the paramount importance of infection reporting, prevention, and mitigation.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764456","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}

引用次数: 0

Redefining Quality in Cell and Gene Therapies: Lessons from Implementing Electronic QMS in Academic cGMP Facility.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-31 DOI: 10.1016/j.ymthe.2025.03.050

Xia Wu, Amaia Cadinanos-Garai, Vivian Quach, Eric Jurado, Alix Vaissié, Mohamed Abou-El-Enein

{"title":"Redefining Quality in Cell and Gene Therapies: Lessons from Implementing Electronic QMS in Academic cGMP Facility.","authors":"Xia Wu, Amaia Cadinanos-Garai, Vivian Quach, Eric Jurado, Alix Vaissié, Mohamed Abou-El-Enein","doi":"10.1016/j.ymthe.2025.03.050","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.050","url":null,"abstract":"Manufacturing cell and gene therapies (CGTs) involves complex processes that require robust quality management, especially within academic current Good Manufacturing Practice (cGMP) facilities, where resources are often limited. Traditional paper-based quality management systems (QMS), while initially convenient, often become burdensome, leading to errors, poor traceability, and compliance risks. Electronic Quality Management Systems (eQMS) are gaining recognition for their ability to centralize and automate key quality processes, significantly enhancing operational efficiency. Through an in-depth case study of the USC/CHLA academic cGMP facility, this review demonstrates tangible improvements achieved by adopting an eQMS. Practical insights gained from this experience are shared, including careful selection of eQMS platforms, phased rollout strategies, and comprehensive staff training. The review also addresses common implementation challenges and suggests practical solutions to overcome them. Lessons learned and strategies discussed here can serve as valuable guidance for other academic institutions considering eQMS adoption. Ultimately, adopting an eQMS equips academic CGT manufacturers to enhance sustainability, continuously optimize operations, and strengthen their strategic position within this rapidly evolving field.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764457","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}

引用次数: 0

TNFAIP8L2 maintains Hair cell function and Regulates Age-related hearing loss via mTORC1 Signaling.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-30 DOI: 10.1016/j.ymthe.2025.03.046

Wen Li, Yu Li, Min Wang, Hao Liu, Guodong Hong, Luhan Jiang, Ziyi Liu, Yunhao Wu, Liangjie Yuan, Xiaoxu Zhao, Zuhong He, Siwei Guo, Yu Xiao, Xiuli Bi, Ming Xia, Guichang Zou, Lining Zhang, Jiangang Gao, Xiaolong Fu

{"title":"TNFAIP8L2 maintains Hair cell function and Regulates Age-related hearing loss via mTORC1 Signaling.","authors":"Wen Li, Yu Li, Min Wang, Hao Liu, Guodong Hong, Luhan Jiang, Ziyi Liu, Yunhao Wu, Liangjie Yuan, Xiaoxu Zhao, Zuhong He, Siwei Guo, Yu Xiao, Xiuli Bi, Ming Xia, Guichang Zou, Lining Zhang, Jiangang Gao, Xiaolong Fu","doi":"10.1016/j.ymthe.2025.03.046","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.046","url":null,"abstract":"Age-related hearing loss (ARHL) is one of the most prevalent and complex disorders. Our previous study demonstrated that abnormal activation of mTORC1 signaling in the cochlear neurosensory epithelium (NSE) causes auditory hair cell damage and contributes to ARHL. However, the underlying mechanism of mTORC1 activation remains unclear. In this study, we identified TNF-alpha-induced protein 8-like 2 (TNFAIP8L2), an immune regulatory gene, as a potential candidate. To elucidate the effect of TNFAIP8L2 on mTORC1 signaling in the NSE and on hearing function, we generated a Tnfaip8l2-deficient (Tnfaip8l2-/-) mouse model. We discovered that Tnfaip8l2-deficiency led to features of oxidative stress in cochlear hair cells and age-related hearing degeneration, exhibiting a similar phenotype to the mTORC1-overactivated Tsc1-cKO mice described previously. Furthermore, rapamycin, a well-known mTORC1 inhibitor, significantly mitigated the hearing dysfunction caused by Tnfaip8l2-deficiency. Mechanistically, we found that TNFAIP8L2 regulates mTORC1 signaling by simultaneously inhibiting the GTPase activity of RHEB and RAC1. Notably, both RHEB and RAC1 inhibitors alleviated the hearing phenotype observed in Tnfaip8l2-/- mice by inhibiting mTORC1 signaling. Collectively, our results provide insights into the activation of the mTORC1 pathway in aged mouse cochleae and positions TNFAIP8L2 as a valuable theoretical strategy.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753682","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}

引用次数: 0

Genome Editing Strategies for Targeted Correction of β-globin Mutation in Sickle Cell Disease: From Bench to Bedside.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-30 DOI: 10.1016/j.ymthe.2025.03.047

Henna Butt, Shruti Sathish, Evan London, Taylor Lee Johnson, Khaled Essawi, Alexis Leonard, John F Tisdale, Selami Demirci

{"title":"Genome Editing Strategies for Targeted Correction of β-globin Mutation in Sickle Cell Disease: From Bench to Bedside.","authors":"Henna Butt, Shruti Sathish, Evan London, Taylor Lee Johnson, Khaled Essawi, Alexis Leonard, John F Tisdale, Selami Demirci","doi":"10.1016/j.ymthe.2025.03.047","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.047","url":null,"abstract":"Sickle cell disease (SCD) includes a range of genotypes that result in a clinical syndrome, where abnormal red blood cell (RBC) physiology leads to widespread complications affecting nearly every organ system. Treatment strategies for SCD can be broadly categorized into disease-modifying therapies and those aimed toward a cure. Although several disease-modifying drugs have been approved, they do not fully address the complexity and severity of SCD. Recent advances in allogeneic transplantation and autologous gene therapy show promising outcomes in terms of efficacy and safety. While these approaches have improved the lives of many patients, achieving a durable and comprehensive cure for all remains challenging. To address this, gene-editing technologies, including zinc finger nucleases, TALENs, CRISPR-Cas, base editing, and prime editing, have been explored both ex vivo and in vivo for targeted correction of the β-globin gene (HBB) in SCD. However, direct correction of HBB and its translation from the laboratory to the clinic presents ongoing limitations, with challenges involved in achieving robust mutation correction efficiency, off-target effects, and high costs of therapies. The optimal strategy for curing SCD remains uncertain, but several promising approaches are emerging. This review will touch on past, present and future developments in HBB correction.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753680","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}

引用次数: 0

A Precision Medicine Approach to Primary Immunodeficiency Disease: Ataluren Strikes Nonsense Mutations Once Again.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-28 DOI: 10.1016/j.ymthe.2025.03.045

Laura Lentini, Riccardo Perriera, Federica Corrao, Raffaella Melfi, Marco Tutone, Pietro S Carollo, Ignazio Fiduccia, Andrea Pace, Davide Ricci, Francesco Genovese, Alain Colige, Philippe Delvenne, Bodo Grimbacher, Michel Moutschen, Ivana Pibiri

{"title":"A Precision Medicine Approach to Primary Immunodeficiency Disease: Ataluren Strikes Nonsense Mutations Once Again.","authors":"Laura Lentini, Riccardo Perriera, Federica Corrao, Raffaella Melfi, Marco Tutone, Pietro S Carollo, Ignazio Fiduccia, Andrea Pace, Davide Ricci, Francesco Genovese, Alain Colige, Philippe Delvenne, Bodo Grimbacher, Michel Moutschen, Ivana Pibiri","doi":"10.1016/j.ymthe.2025.03.045","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.045","url":null,"abstract":"Primary Immunodeficiency Diseases (PIDs) are associated with multiple genetic alterations including mutations of the LPS responsive Beige anchor (LRBA) gene. Nonsense mutations in the LRBA gene resulting in premature termination codons cause the loss of LRBA protein expression in PID. We evaluated the impact of a translational readthrough-inducing drug (TRID) ataluren as a nonsense suppression therapy in a PID patient with a homozygous stop codon mutation in exon 30 of LRBA. A precision medicine approach allowed us to pass from \"in silico\" to \"in vitro\" to the \"bedside\": following the in vitro treatment of patient-derived primary fibroblasts with ataluren, we observed a restoration of the LRBA protein expression and localization. In silico predictions suggested LRBA retained function after readthrough. Based on the successful experimental and computational results we treated the patient with ataluren resulting in an improvement of his clinical symptoms and quality of life. Importantly, the clinical symptoms were associated with a recovery of LRBA expression in liver biopsies post-treatment compared to pre-treatment. Our results provide a proof-of-concept demonstrating that ataluren, can rescue LRBA expression in PID. This work highlights the potential for personalized precision medicine approaches to be exploited for different genetic diseases due to premature termination codons.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753678","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}

引用次数: 0

Urine-derived stem cells display homing, incorporation, and regeneration in human organoid and mouse models of acute kidney injury.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-28 DOI: 10.1016/j.ymthe.2025.03.044

Julie Bejoy, Richard C Welch, Eddie S Qian, Felisha M Williams, Katherine N Gibson-Corley, Matthew H Wilson, Neal Paragas, Lauren E Woodard

{"title":"Urine-derived stem cells display homing, incorporation, and regeneration in human organoid and mouse models of acute kidney injury.","authors":"Julie Bejoy, Richard C Welch, Eddie S Qian, Felisha M Williams, Katherine N Gibson-Corley, Matthew H Wilson, Neal Paragas, Lauren E Woodard","doi":"10.1016/j.ymthe.2025.03.044","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.044","url":null,"abstract":"Urine-derived stem cells (USCs) are adult human stem cells that can be collected noninvasively from urine and cultured in vitro. Because of their renal origin and reported therapeutic effects, we hypothesized that USCs would home to the injured kidney in acute kidney injury (AKI) models. We employed mouse models of glycerol-induced rhabdomyolysis or unilateral nephrectomy with clamping ischemia reperfusion injury to model AKI. To track USC homing by live animal imaging, we administered luciferase-expressing USCs to mice by intraperitoneal injection. We observed USC localization to both the tubules and glomeruli of injured mice within three hours by histology. We confirmed the presence of luciferase-expressing (Luc) USCs in the kidney at 3 h, 24 h, and 48 h after the injection using biodistribution analysis of quantitative bioluminescence tomography (qBLT) imaging. We performed immunostaining for kidney injury molecule-1 (KIM-1) for kidney injury and found reduced expression in USC-treated group at 24 h after injection. To evaluate the effects of the human USCs on injured human nephrons, we injured human kidney organoids with the nephrotoxin cisplatin (5 μM) followed by 5x104 USCs treatment. USCs were incorporated and lowered expression of KIM-1 in the organoids. In conclusion, USCs home to injured nephrons and reduce measures of kidney injury.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753684","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}

引用次数: 0

Clinical development of allogeneic chimeric antigen receptor αβ-T Cells.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-27 DOI: 10.1016/j.ymthe.2025.03.040

Christos Georgiadis, Roland Preece, Waseem Qasim

{"title":"Clinical development of allogeneic chimeric antigen receptor αβ-T Cells.","authors":"Christos Georgiadis, Roland Preece, Waseem Qasim","doi":"10.1016/j.ymthe.2025.03.040","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.040","url":null,"abstract":"Ready-made banks of allogeneic chimeric antigen receptor (CAR) T cells, produced to be available at the time of need, offer the prospect of accessible and cost-effective cellular therapies. Various strategies have been developed to overcome allogeneic barriers, drawing on cell engineering platforms including RNA interference, protein-based restriction and genome editing, including RNA-guided CRISPR-Cas and base editing tools. Alloreactivity and the risk of graft versus host disease from non-matched donor cells have been mitigated by disruption of αβ-T cell receptor expression on the surface of T cells, and stringent removal of any residual αβ-T cell populations. In addition, host mediated rejection has been tackled through a combination of augmented lymphodepletion and cell engineering strategies that have allowed infused cells to evade immune recognition or conferred resistance to lymphodepleting agents to promote persistence and expansion of effector populations. Early phase studies using 'off-the shelf' universal donor CAR T cells have been undertaken mainly in the context of blood malignancies, where emerging data of clinical responses have supported wider adoption and further applications. These developments offer the prospect of alternatives to current autologous approaches through the emerging application of genome engineering solutions to improve safety, persistence and function of universal donor products.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743064","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}

引用次数: 0