Molecular Therapy最新文献_第4页

Understanding the interplay between oHSV and the host immune system: Implications for therapeutic oncolytic virus development. 了解oHSV与宿主免疫系统之间的相互作用：对溶瘤病毒治疗发展的影响。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 Epub Date: 2024-12-30 DOI: 10.1016/j.ymthe.2024.12.054

Kalkidan Ayele, Hiroaki Wakimoto, Hans J Nauwynck, Howard L Kaufman, Samuel D Rabkin, Dipongkor Saha

{"title":"Understanding the interplay between oHSV and the host immune system: Implications for therapeutic oncolytic virus development.","authors":"Kalkidan Ayele, Hiroaki Wakimoto, Hans J Nauwynck, Howard L Kaufman, Samuel D Rabkin, Dipongkor Saha","doi":"10.1016/j.ymthe.2024.12.054","DOIUrl":"10.1016/j.ymthe.2024.12.054","url":null,"abstract":"Oncolytic herpes simplex viruses (oHSV) preferentially replicate in cancer cells while inducing antitumor immunity, and thus, they are often referred to as in situ cancer vaccines. OHSV infection of tumors elicits diverse host immune responses comprising both innate and adaptive components. Although the innate and adaptive immune responses primarily target the tumor, they also contribute to antiviral immunity, limiting viral replication/oncolysis. OHSV-encoded proteins use various mechanisms to evade host antiviral pathways and immune recognition, favoring oHSV replication, oncolysis, and spread. In general, oHSV infection and replication within tumors results in a series of sequential events, such as oncolysis and release of tumor and viral antigens, dendritic cell-mediated antigen presentation, T cell priming and activation, T cell trafficking and infiltration to tumors, and T cell recognition of cancer cells, leading to tumor (and viral) clearance. These sequential events align with all steps of the cancer-immunity cycle. However, a comprehensive understanding of the interplay between oHSV and host immune responses is crucial to optimize oHSV-induced antitumor immunity and efficacy. Therefore, this review aims to elucidate oHSV's communication with innate and adaptive immune systems and use such interactions to improve oHSV's potential as a potent immunovirotherapeutic agent against cancer.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"1327-1343"},"PeriodicalIF":12.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915331","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

Antisense-mediated exon skipping targeting EZH2 suppresses tumor growth in a xenograft mouse model of hepatocellular carcinoma. 靶向EZH2的反义介导外显子跳变抑制肝癌小鼠异种移植模型的肿瘤生长

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 Epub Date: 2025-02-22 DOI: 10.1016/j.ymthe.2025.02.032

Jialin Bai, Bolin Zhao, Yongkun Ma, Li Wang, Pengchao Feng, Yimin Hua

{"title":"Antisense-mediated exon skipping targeting EZH2 suppresses tumor growth in a xenograft mouse model of hepatocellular carcinoma.","authors":"Jialin Bai, Bolin Zhao, Yongkun Ma, Li Wang, Pengchao Feng, Yimin Hua","doi":"10.1016/j.ymthe.2025.02.032","DOIUrl":"10.1016/j.ymthe.2025.02.032","url":null,"abstract":"Enhancer of zeste homolog 2 (EZH2) catalyzes trimethylation of histone H3 at lysine 27 (H3K27me3), which promotes heterochromatin formation and gene silencing. Expression of EZH2 is frequently elevated in various malignancies, including hepatocellular carcinoma (HCC). Silencing of EZH2 has been pursued as a promising strategy to halt cancer progression. Here, we identified antisense oligonucleotides (ASOs) that efficiently silence EZH2 through promoting skipping of its exon 14, an exon encoding part of the essential CXC domain, increasing production of an internally shortened isoform that exerts dominant negative effect on the full-length EZH2. A lead ASO, hybridizing to an exonic splicing enhancer element bound by SRSF3, robustly promoted exon 14 skipping not only in cultured human HCC cell lines but also in mouse peripheral tissues after systemic administration, leading to dramatic reduction of EZH2 and H3K27me3 levels. The lead ASO potently inhibited HCC cell proliferation through multiple mechanisms including enhanced apoptosis, cell-cycle arrest, and reversed epithelial-mesenchymal transition, which is likely attributable to the suppression of diverse cancer-related pathways. In an orthotopic xenograft HCC mouse model, ASO treatment repressed tumor growth, improved tissue phenotype, and extended the median survival. Our data highlight therapeutic potential of the lead exon-skipping ASO in treating HCC.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"1485-1501"},"PeriodicalIF":12.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483709","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

RESET: A TCR-coupled antigen receptor with superior targeting sensitivity and reversible drug-regulated anti-tumor activity. RESET：一种可逆的tcr偶联抗原受体，具有优越的靶向敏感性和药理学控制的抗肿瘤活性。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 Epub Date: 2025-02-20 DOI: 10.1016/j.ymthe.2025.02.026

Jardin Leleux, Jillian Rosenberg, Olmo Sonzogni, Rebecca L Walker, Anita Venkitaraman, Sarah M Garrison, Nan Jin, Philip D Gregory, Jordan Jarjour

{"title":"RESET: A TCR-coupled antigen receptor with superior targeting sensitivity and reversible drug-regulated anti-tumor activity.","authors":"Jardin Leleux, Jillian Rosenberg, Olmo Sonzogni, Rebecca L Walker, Anita Venkitaraman, Sarah M Garrison, Nan Jin, Philip D Gregory, Jordan Jarjour","doi":"10.1016/j.ymthe.2025.02.026","DOIUrl":"10.1016/j.ymthe.2025.02.026","url":null,"abstract":"Chimeric antigen receptor (CAR) T cells are effective cancer therapies, particularly in indications with high, stable, and tumor-specific antigen expression. Other settings may require improved targeting sensitivity, controllable targeting selectivity, and/or additional potency enhancements to achieve robust efficacy. Here, we describe a novel receptor architecture called RESET (rapamycin-enabled, switchable endogenous T cell receptor) that combines (1) cell surface antigen targeting, (2) small-molecule regulation, and (3) the signaling proficiency and inherent sensitivity of native T cell receptors. RESET-T cells outperformed both constitutive and drug-regulated CAR-T cells and show hallmarks of TCR activation that suggest improved fidelity to native T cell responses. Pharmacological control then increases safety through toggling T cell activation between active and resting states and may mitigate T cell exhaustion caused by continuous antigen exposure. This convergence of drug-regulated targeting and natural immune receptor signal transduction may better replicate the kinetics and physiology of a classical T cell response and potentiate more successful and safer immunotherapies.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"1608-1620"},"PeriodicalIF":12.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468069","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

Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells. 将“废弃”的基因组位点转化为整合T细胞和NK细胞中的嵌合抗原受体的宝贵位点。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 Epub Date: 2025-02-20 DOI: 10.1016/j.ymthe.2025.02.028

Yajie Wang, Jie Jiang, Kai Shang, Xiaobao Xu, Jie Sun

{"title":"Turning \"trashed\" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.","authors":"Yajie Wang, Jie Jiang, Kai Shang, Xiaobao Xu, Jie Sun","doi":"10.1016/j.ymthe.2025.02.028","DOIUrl":"10.1016/j.ymthe.2025.02.028","url":null,"abstract":"Chimeric antigen receptor (CAR)-based immune cell therapy involves genetically engineering immune cells, such as T cells and natural killer (NK) cells, to express CARs that can specifically recognize target antigens. This modification enables T/NK cells to selectively eliminate tumor cells following adoptive transfer. One common approach to stably integrate CARs into the genome of T/NK cells is through retroviral or lentiviral vectors. However, these vectors mediate semi-random gene integration, posing risks such as oncogenic mutations, gene silencing, and variable CAR expression levels. Targeted integration of CAR genes into the specific genomic locus could overcome these limitations, but identifying the optimal integration sites to maximize the safety and efficacy of CAR-T/NK cell products remains a critical question. Improper integration sites may disturb the endogenous genes surrounding the integration sites, raising safety concerns. Additionally, regulatory elements at the integration sites, such as promoters, can influence the expression level of CAR genes, thus affecting the efficacy of CAR-T/NK cells. In this review, we summarized current strategies for selecting integration sites and promoters in the engineering of CAR-T/NK cells to achieve potent anti-tumor efficacy in preclinical studies.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"1368-1379"},"PeriodicalIF":12.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468414","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

Dysregulation of astrocyte-derived matrix gla protein impairs dendritic spine development in pyridoxine-dependent epilepsy. 星形胶质细胞衍生基质Gla蛋白的失调损害吡哆醇依赖性癫痫的树突脊柱发育。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 Epub Date: 2025-02-20 DOI: 10.1016/j.ymthe.2025.02.027

Junjie Wu, Dezhe Qin, Ziqi Liang, Qiang Liu, Min Wang, Ye Guo, Weixiang Guo

{"title":"Dysregulation of astrocyte-derived matrix gla protein impairs dendritic spine development in pyridoxine-dependent epilepsy.","authors":"Junjie Wu, Dezhe Qin, Ziqi Liang, Qiang Liu, Min Wang, Ye Guo, Weixiang Guo","doi":"10.1016/j.ymthe.2025.02.027","DOIUrl":"10.1016/j.ymthe.2025.02.027","url":null,"abstract":"In spite of adequate seizure control, approximately 75% of pyridoxine-dependent epilepsy (PDE) patients with ALDH7A1 mutation still suffer from intellectual disability. However, the mechanisms underlying brain dysfunction in PDE patients are still unknown even when seizure control is achieved. In this study, we show that mice with specific deletion of Aldh7a1 from astrocytes, but not neurons, exhibit PDE, and have defective dendritic spine development and cognitive impairment when seizure occurrence is well controlled. Mechanistically, ALDH7A1 deficiency leads to dysregulation of astrocyte-derived matrix gla protein (MGP), one of the vitamin K-dependent proteins, thereby impairing dendritic spine development and synaptic transmission. Notably, supplementation of menaquinone-7, a form of vitamin K, promotes MGP activation and rescues defective dendritic spine development, abnormal synaptic transmission, and cognitive impairment in Aldh7a1-deficient mice. Therefore, our findings not only unravel the important role of ALDH7A1 in astrocytes contributing to the pathogenesis of PDE, but also provide a potential therapeutic intervention to ameliorate cognitive impairment in PDE beyond pyridoxine treatment.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"1785-1802"},"PeriodicalIF":12.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468132","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 BPTF-specific PROTAC degrader enhances NK cell-based cancer immunotherapy. 一种bptf特异性的PROTAC降解物增强了基于NK细胞的癌症免疫治疗。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 Epub Date: 2025-02-11 DOI: 10.1016/j.ymthe.2025.02.013

Yunjia Li, Lin Bai, Hao Liang, Peidong Yan, Hao Chen, Zhuoxian Cao, Yiqing Shen, Zhongyv Wang, Mei Huang, Bin He, Quan Hao, Yide Mei, Haiming Wei, Chen Ding, Jing Jin, Yi Wang

引用次数: 0

Dasatinib-resistant universal CAR-T cells proliferate in the presence of host immune cells and exhibit antitumor activity. 抗达沙替尼通用CAR-T细胞在宿主免疫细胞存在下增殖并表现出抗肿瘤活性

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 Epub Date: 2025-02-11 DOI: 10.1016/j.ymthe.2025.02.012

Yuhang Cheng, Jiayuan Zhang, Wei Mu, Shanwei Ye, Jiali Cheng, Li Zhu, Gaoxiang Wang, Yang Cao, Dengju Li, Guang Hu, Liang Huang, Jue Wang, Jianfeng Zhou

{"title":"Dasatinib-resistant universal CAR-T cells proliferate in the presence of host immune cells and exhibit antitumor activity.","authors":"Yuhang Cheng, Jiayuan Zhang, Wei Mu, Shanwei Ye, Jiali Cheng, Li Zhu, Gaoxiang Wang, Yang Cao, Dengju Li, Guang Hu, Liang Huang, Jue Wang, Jianfeng Zhou","doi":"10.1016/j.ymthe.2025.02.012","DOIUrl":"10.1016/j.ymthe.2025.02.012","url":null,"abstract":"The universal chimeric antigen receptor T cell (UCAR-T) immunotherapy derived from healthy donors holds great promise in pan-cancer treatment. However, UCAR-T cell therapy faces a challenge in the rapid elimination of allogeneic cells by the host immune system. To address this, we introduced a T316I mutation in the leukocyte-specific protein tyrosine kinase (LCK) locus in CAR-T cells using the cytosine base editor (CBE) system. Concurrently, we disrupted endogenous T cell receptor alpha chain (TRAC) and beta-2 microglobulin (B2M) with the CRISPR-Cas9 system, along with dasatinib to overcome host immune rejection, an Src family kinase (SFK) inhibitor. The resulting LCK mutated UCAR-T (KM UCAR-T) cells exhibited normal phenotypes in activation, proliferation, differentiation, and tumor cytotoxicity in vitro. Moreover, KM UCAR-T cells demonstrated sustained expansion in mixed lymphocyte reactions (MLR) when incubated with T cells or peripheral blood mononuclear cells (PBMCs) from HLA-mismatched donors upon dasatinib treatment. Additionally, we illustrated that KM UCAR-T cells displayed antitumor activity in a xenograft murine model and verified the expansion and cytotoxicity of KM UCAR-T over traditional UCAR-T in the presence of allogeneic PBMCs when treated with dasatinib in vivo. These findings offer a novel strategy for UCAR-T cells to resist host immune rejection and achieve sustained expansion.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"1535-1551"},"PeriodicalIF":12.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399698","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

Gene therapy rescues brain edema and motor function in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts. 基因疗法拯救了巨脑白质脑病伴皮层下囊肿小鼠模型的脑水肿和运动功能。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 Epub Date: 2025-03-05 DOI: 10.1016/j.ymthe.2025.02.046

Alejandro Brao, Ángela Sánchez, Irina Rodríguez, Javier Del Rey, Silvia Lope-Piedrafita, Esther Prat, Virginia Nunes, Miguel Chillón, Raúl Estévez, Assumpció Bosch

{"title":"Gene therapy rescues brain edema and motor function in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts.","authors":"Alejandro Brao, Ángela Sánchez, Irina Rodríguez, Javier Del Rey, Silvia Lope-Piedrafita, Esther Prat, Virginia Nunes, Miguel Chillón, Raúl Estévez, Assumpció Bosch","doi":"10.1016/j.ymthe.2025.02.046","DOIUrl":"10.1016/j.ymthe.2025.02.046","url":null,"abstract":"Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an ultrarare, infantile-onset leukodystrophy characterized by white matter edema for which there is no treatment. More than 75% of diagnosed cases result from biallelic loss-of-function mutations in the astrocyte-specific gene MLC1, leading to early-onset macrocephaly, cerebellar ataxia, epilepsy, and mild cognitive decline. To develop a gene therapy for MLC, we administered an adeno-associated viral vector capable of crossing the murine blood-brain barrier, delivering the human MLC1 cDNA under the control of a human astrocyte-specific promoter, to 10-month-old Mlc1-/- mice. We observed long-term astrocyte-driven expression of MLC1 up to 1 year after viral vector administration in all brain areas analyzed. Despite the late-stage intervention, in vivo magnetic resonance imaging revealed normalization of water accumulation. Notably, our therapy successfully reversed locomotor deficits in Mlc1-/- mice, as evidenced by improved performance in motor tests assessing cerebellar ataxia-like behaviors. Collectively, these findings not only demonstrate the sustained efficacy of our gene therapy but also highlight the reversibility of vacuolation and motor impairments in Mlc1-/- mice, suggesting that MLC patients could benefit from treatment even after symptom onset.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"1434-1448"},"PeriodicalIF":12.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573497","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

Y4 RNA fragment alleviates myocardial injury in heart transplantation via SNRNP200 to enhance IL-10 mRNA splicing. Y4 RNA片段通过snrnp200介导的IL-10 pre-mRNA剪接增强减轻心脏移植心肌缺血-再灌注损伤。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 Epub Date: 2025-02-11 DOI: 10.1016/j.ymthe.2025.02.014

Chuanghong Lu, Zhongyuan Meng, Senhu Tang, Heng Wei, Yaoshi Hu, Dexin Chen, Dezhao Liu, Hong Wen, Kun Dong, Na Na, Feng Huang, Zhiyu Zeng

{"title":"Y4 RNA fragment alleviates myocardial injury in heart transplantation via SNRNP200 to enhance IL-10 mRNA splicing.","authors":"Chuanghong Lu, Zhongyuan Meng, Senhu Tang, Heng Wei, Yaoshi Hu, Dexin Chen, Dezhao Liu, Hong Wen, Kun Dong, Na Na, Feng Huang, Zhiyu Zeng","doi":"10.1016/j.ymthe.2025.02.014","DOIUrl":"10.1016/j.ymthe.2025.02.014","url":null,"abstract":"Myocardial ischemia-reperfusion injury (MIRI) inevitably occurs during heart transplantation, highlighting the imperative for effective therapeutic interventions. A Y4 RNA fragment (YF1) was applied to treat a syngeneic mouse model of heart transplantation, with the heart subjected to cold ischemia-reperfusion (CIR). Cardiomyocytes and macrophages were treated with YF1, and a cellular cold hypoxia-reoxygenation (CHR) model was established. We found that YF1 alleviated CIR-induced inflammatory macrophage infiltration and cardiomyocytes injury in the graft heart. YF1 had no direct effects on cardiomyocytes in vitro, while YF1 inhibited macrophage polarization to the pro-inflammatory phenotype with increased expression of anti-inflammatory factors. Moreover, YF1 attenuated CHR-induced cardiomyocyte injury by regulating the interleukin-10 (IL-10) expression in macrophages. Mechanistically, YF1 increased the mRNA expression ratio of IL-10/pre-IL-10 by binding to SNRNP200, a spliceosome-specific protein for pre-mRNA splicing, with reduced SNRNP200 ubiquitination. It was reversed by Brr2-IN-3, a specific SNRNP200 inhibitor. Collectively, we hold that YF1 might alleviate MIRI in heart transplantation via binding to SNRNP200 and regulating its ubiquitination to enhance IL-10 pre-mRNA splicing. These findings further clarify the effects and mechanism of YF1 on MIRI and suggest a potential cardioprotective therapy in heart transplantation.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"1735-1748"},"PeriodicalIF":12.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399700","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

How to democratize cell and gene therapy: a global approach. 如何使细胞和基因治疗民主化：全球方法。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-02 DOI: 10.1016/j.ymthe.2025.03.061

Rayne H Rouce, Bambi J Grilley

{"title":"How to democratize cell and gene therapy: a global approach.","authors":"Rayne H Rouce, Bambi J Grilley","doi":"10.1016/j.ymthe.2025.03.061","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.061","url":null,"abstract":"Over the past 25 years, the field of cell and gene therapy has grown substantially, with almost 50 therapies approved in the U.S. to treat severe, often life-threatening diseases. Despite clinical successes, the high costs and complex manufacturing and delivery requirements of cell and gene therapies (CGT) present significant challenges to their broad use and equitable access. Disparities in access to CGT range from financial constraints to infrastructure limitations and regulatory hurdles. As CGT trials expand globally, innovative strategies are needed to address these inequities, including alternative manufacturing models, harmonizing regulatory requirements, and innovative payment structures to replace the high up-front cost of current treatments. Addressing barriers like lack of infrastructure, such as stem cell processing and specialized personnel, will be necessary to increase global CGT access and requires a multi-stakeholder approach. Academic, pharmaceutical, government, and nonprofit entities must cooperate to develop a more sustainable model for CGT. Additionally, new university-led and public-private partnerships aim to facilitate access in underserved populations. To achieve equitable global access, a comprehensive strategy must involve innovative manufacturing, education, regulatory alignment, and stakeholder engagement, while ensuring that CGTs are both accessible and affordable to those who would benefit most.","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":"143780232","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