Molecular Therapy最新文献_第10页

Precise Progerin Targeting Using RfxCas13d: A Therapeutic Avenue for Hutchinson-Gilford Progeria Syndrome. 利用RfxCas13d精确靶向早衰蛋白：Hutchinson-Gilford早衰综合征的治疗途径

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-14 DOI: 10.1016/j.ymthe.2025.06.017

Unbin Chae,Hae-Jun Yang,Hanseop Kim,Seung Hwan Lee,Dong Gil Lee,Jeong Young Koo,Seung-Min Ha,Seo-Jong Bak,Mina Joo,Hyun Hee Nam,Kyung-Seob Lim,Philyong Kang,Hee-Chang Son,You Jeong An,Young-Hyun Kim,In-Sung Song,Sang-Hee Lee,Hae Rim Kim,Sang-Mi Cho,Eun-Kyoung Kim,Ki-Hoan Nam,Kyung-Sook Chung,Jae-Yoon Kim,Seon-Yeop Kim,Seon-Kyu Kim,Seon-Young Kim,Dong-Seok Lee,Jin-Man Kim,Young-Ho Park,Sun-Uk Kim

{"title":"Precise Progerin Targeting Using RfxCas13d: A Therapeutic Avenue for Hutchinson-Gilford Progeria Syndrome.","authors":"Unbin Chae,Hae-Jun Yang,Hanseop Kim,Seung Hwan Lee,Dong Gil Lee,Jeong Young Koo,Seung-Min Ha,Seo-Jong Bak,Mina Joo,Hyun Hee Nam,Kyung-Seob Lim,Philyong Kang,Hee-Chang Son,You Jeong An,Young-Hyun Kim,In-Sung Song,Sang-Hee Lee,Hae Rim Kim,Sang-Mi Cho,Eun-Kyoung Kim,Ki-Hoan Nam,Kyung-Sook Chung,Jae-Yoon Kim,Seon-Yeop Kim,Seon-Kyu Kim,Seon-Young Kim,Dong-Seok Lee,Jin-Man Kim,Young-Ho Park,Sun-Uk Kim","doi":"10.1016/j.ymthe.2025.06.017","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.017","url":null,"abstract":"Hutchinson-Gilford progeria syndrome (HGPS), an extremely rare progressive genetic disorder, is caused by a point mutation in LMNA that induces progerin production, which disrupts cellular function and triggers premature aging and mortality. Despite extensive efforts, HPGS remains incurable. We successfully implemented a strategy using RfxCas13d to selectively target progerin mRNA at specific junction regions, without unintended cleavage and reduce its expression. This technique discriminated between normal lamin A and progerin, thus providing a safe and targeted therapeutic avenue to treat HGPS. Our approach effectively restored aberrant gene expression and progerin-induced cellular phenotypes, including senescence, mitochondrial dysfunction, and DNA damage in cells with HGPS and LMNAG608G/G608G mice. Notably, LMNAG608G/G608G mice exhibited improved progeroid phenotypes, suggesting a potential therapeutic application of this approach for other diseases resulting from abnormal RNA splicing.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"44 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295865","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 single dose of a vectorized mAb targeting TDP-43 potently inhibits the neuropathology in a model of ALS/FTD. 单剂量靶向TDP-43的矢量化单抗可有效抑制ALS/FTD模型中的神经病理学。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-14 DOI: 10.1016/j.ymthe.2025.06.026

Greg Del Val,Florence Gauye,Mickaël Audrain,Sébastien Menant,Monisha Ratnam,Elodie Chevalier,Romain Ollier,Daisy Bhatia,Tamara Seredenina,Tariq Afroz,Andrea Pfeifer,Marie Kosco-Vilbois,Damien Nevoltris

{"title":"A single dose of a vectorized mAb targeting TDP-43 potently inhibits the neuropathology in a model of ALS/FTD.","authors":"Greg Del Val,Florence Gauye,Mickaël Audrain,Sébastien Menant,Monisha Ratnam,Elodie Chevalier,Romain Ollier,Daisy Bhatia,Tamara Seredenina,Tariq Afroz,Andrea Pfeifer,Marie Kosco-Vilbois,Damien Nevoltris","doi":"10.1016/j.ymthe.2025.06.026","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.026","url":null,"abstract":"TAR DNA binding protein-43 (TDP-43)-mediated pathology is a hallmark of devastating neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Thus, monoclonal antibodies (mAbs) are being developed to target the pathological forms of this protein. To improve mAb exposure within the central nervous system, a potent anti-TDP-43 mAb, ACI-5891, was generated as a vectorized full-length antibody (vmAb) and evaluated for brain delivery using adeno-associated virus 9 (AAV9). Among the expression cassettes explored, the selected construct utilized an internal ribosome entry site (IRES), which produced high expression yields in vitro (>200 mg/L) with comparable quality, binding and functional properties to the conventionally produced mAb. A single intracisternal administration of vmAb ACI-5891 demonstrated a broad brain distribution and sustained expression (i.e., months) in the serum, cerebrospinal fluid and brain of mice. In a mouse model of ALS/FTD, treatment with a vmAb reduced the amount of pathological phospho-TDP-43 in neurons by 58% and 68% when expressed either using a ubiquitous promoter or a brain-selective promoter, respectively. This innovative approach sufficiently delivers effective immunotherapy with a single dose and illustrates the enormous potential of using vectorized antibodies to target neuropathology, including TDP-43 in patients suffering from ALS, FTD and other TDP-43 proteinopathies.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"7 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295860","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

Nebulization of a mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi. 一种mrna编码单克隆抗体雾化用于马驹被动免疫马红球菌。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-14 DOI: 10.1016/j.ymthe.2025.06.025

Rebecca M Legere,Jeannine A Ott,Cristina Poveda,Daryll Vanover,Karin E R Borba,Cameron L Martin,Bibiana P da Silveira,Jocelyne M Bray,Kerstin Landrock,Gus A Wright,J Chistensen Blazier,Andrew E Hillhouse,Ashley L Benham-Duret,Brandon Mistretta,Rafaela L Klein,Sarah M Thompson,Amelia R Woolums,Michael F Criscitiello,Luc R Berghman,Angela I Bordin,Phillip J Santangelo,Jeroen Pollet,Noah D Cohen

{"title":"Nebulization of a mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi.","authors":"Rebecca M Legere,Jeannine A Ott,Cristina Poveda,Daryll Vanover,Karin E R Borba,Cameron L Martin,Bibiana P da Silveira,Jocelyne M Bray,Kerstin Landrock,Gus A Wright,J Chistensen Blazier,Andrew E Hillhouse,Ashley L Benham-Duret,Brandon Mistretta,Rafaela L Klein,Sarah M Thompson,Amelia R Woolums,Michael F Criscitiello,Luc R Berghman,Angela I Bordin,Phillip J Santangelo,Jeroen Pollet,Noah D Cohen","doi":"10.1016/j.ymthe.2025.06.025","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.025","url":null,"abstract":"Inhalation of Rhodococcus equi causes severe pneumonia in humans and animals worldwide, most commonly affecting horse foals. The standard for preventing R. equi pneumonia in foals is transfusion of hyperimmune plasma, which is expensive and carries the risk of adverse effects. Our goal was to passively immunize foals against R. equi by nebulizing mRNA encoding an equine monoclonal antibody (mAb) against the virulence associated protein A (VapA) directly into the lungs. VapA-specific memory B-cells from an immunized horse were used to identify and select the sequence for an equine IgG1 mAb. In vitro transcribed mRNA encoding this sequence expressed full-length, VapA-specific mAbs in vitro, and safely and effectively produced intrapulmonary mAb in foals for at least 5 days following nebulization. These findings establish a platform to generate mRNA-encoded mAbs for immunotherapeutic and immunoprophylactic applications in horses and demonstrate the feasibility of delivering nebulized mRNA-mAb for intrapulmonary mAb expression in neonates.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"228 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295806","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

mRNA-LNP vaccines against hepatitis B virus induce protective immune responses in preventive and chronic mouse challenge models. 乙型肝炎病毒mRNA-LNP疫苗在预防和慢性小鼠攻击模型中诱导保护性免疫反应。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-14 DOI: 10.1016/j.ymthe.2025.06.027

María José Limeres, Rocio Gambaro, Malin Svensson, Silvia Fraude-El Ghazi, Leah Pretsch, Daniel Frank, German A Islan, Ignacio Rivero Berti, Matthias Bros, Ying K Tam, Hiromi Muramatsu, Norbert Pardi, Stephan Gehring, Maximiliano L Cacicedo

{"title":"mRNA-LNP vaccines against hepatitis B virus induce protective immune responses in preventive and chronic mouse challenge models.","authors":"María José Limeres, Rocio Gambaro, Malin Svensson, Silvia Fraude-El Ghazi, Leah Pretsch, Daniel Frank, German A Islan, Ignacio Rivero Berti, Matthias Bros, Ying K Tam, Hiromi Muramatsu, Norbert Pardi, Stephan Gehring, Maximiliano L Cacicedo","doi":"10.1016/j.ymthe.2025.06.027","DOIUrl":"10.1016/j.ymthe.2025.06.027","url":null,"abstract":"Over 300 million people worldwide suffer from chronic hepatitis B virus (HBV) infections that can cause serious liver damage and hepatocellular carcinoma. Ineffective innate and adaptive immune responses characterize these chronic infections, making the development of a therapeutic vaccine an urgent medical need. While current vaccines can prevent HBV infections, they are ineffective in treating chronic disease. This study investigated lipid nanoparticle (LNP)-formulated nucleoside-modified mRNA vaccines encoding hepatitis B surface antigen (HBsAg) for prophylactic and therapeutic applications. We found that HBsAg mRNA-LNP vaccines induced robust humoral and cellular immune responses, outperforming the protein-based vaccine approved for human use. The incorporation of a major histocompatibility complex class I (MHC class I) signal peptide further enhanced Th1-biased responses preventing HBV infections in a mouse model. Importantly, mRNA-LNP vaccination led to seroconversion, HBsAg clearance, and strong T cell responses in a chronically infected mouse model. These findings highlight the potential of mRNA-LNP as an alternative and effective vaccine modality for HBV prophylaxis and therapeutic use in treating chronic infections.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302566","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

Therapeutic Effect of Galactosyltransferase- and Sialyltransferase-encoding mRNA in Rheumatoid Arthritis. 半乳糖转移酶和唾液转移酶编码mRNA对类风湿关节炎的治疗作用。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-13 DOI: 10.1016/j.ymthe.2025.06.018

Xinyi Peng,Yingyu Li,Xiu Sun,Guoru Ren,Haojun Li,Xiaocheng Wang,Peng George Wang,Qingwen Wang,Yang Ji

引用次数: 0

Targeting RNA adenosine editing and modification enzymes for RNA therapeutics. 靶向RNA腺苷编辑和修饰酶用于RNA治疗。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-09 DOI: 10.1016/j.ymthe.2025.05.021

Nikolaos I Vlachogiannis, Maria Polycarpou-Schwarz, Aikaterini-Paraskevi Avdi, Simon Tual-Chalot, Konstantinos Stellos

{"title":"Targeting RNA adenosine editing and modification enzymes for RNA therapeutics.","authors":"Nikolaos I Vlachogiannis, Maria Polycarpou-Schwarz, Aikaterini-Paraskevi Avdi, Simon Tual-Chalot, Konstantinos Stellos","doi":"10.1016/j.ymthe.2025.05.021","DOIUrl":"10.1016/j.ymthe.2025.05.021","url":null,"abstract":"Adenosine-to-inosine (A-to-I) RNA editing, and N6 methyladenosine (m6A) are among the most abundant modifications in eukaryotic messenger RNA, affecting various aspects of RNA metabolism and cellular function, including proliferation, differentiation, responses to stressors, and cell death. Recent preclinical evidence suggests that both modifications play a significant role in multiple disorders, including infections, chronic inflammatory diseases, and cancer, sparking great interest in their therapeutic potential. Structural characterization of ADARs (adenosine deaminases acting on RNA) and key m6A enzymes has enabled the development of small molecule inhibitors modulating their expression, enzymatic activity, or binding to target RNAs. Herein, we review preclinical evidence supporting the therapeutic benefits of targeting ADARs and m6A enzymes in diverse disease contexts. Small molecule inhibitors of RNA modification enzymes have shown potent anti-proliferative and pro-apoptotic effects in cancer cells, and have successfully inhibited tumor growth in vivo, without evident toxicity, while their combination with immuno-/chemotherapeutics displayed synergistic anti-neoplastic action. Adenosine RNA editing via recruitment of endogenous ADARs and usage of guide RNAs showed remarkable efficacy in correcting G-to-A point mutations and restoring the associated protein expression with limited off-target activity. Future studies are warranted to evaluate the safety and clinical efficacy of RNA editing or modification-targeting therapeutics in patients.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266805","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

Tailoring capsid-directed evolution technology for improved AAV-mediated CAR-T generation. 定制囊壳定向进化技术，改进 AAV 介导的 CAR-T 生成。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2024-12-12 DOI: 10.1016/j.ymthe.2024.12.012

Adrian Westhaus, Elena Barba-Sarasua, Yuyan Chen, Kenneth Hsu, Suzanne Scott, Maddison Knight, Florencia Haase, Santiago Mesa Mora, Benjamin C Houghton, Ramon Roca-Pinilla, Predrag Kalajdzic, Geraldine O'Neill, Adrian J Thrasher, Giorgia Santilli, Leszek Lisowski

{"title":"Tailoring capsid-directed evolution technology for improved AAV-mediated CAR-T generation.","authors":"Adrian Westhaus, Elena Barba-Sarasua, Yuyan Chen, Kenneth Hsu, Suzanne Scott, Maddison Knight, Florencia Haase, Santiago Mesa Mora, Benjamin C Houghton, Ramon Roca-Pinilla, Predrag Kalajdzic, Geraldine O'Neill, Adrian J Thrasher, Giorgia Santilli, Leszek Lisowski","doi":"10.1016/j.ymthe.2024.12.012","DOIUrl":"10.1016/j.ymthe.2024.12.012","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell (CAR-T) therapies present options for patients diagnosed with certain leukemias. Recent advances of the technology included a method to integrate the CAR into the T cell receptor alpha constant (TRAC) locus to take advantage of the endogenous promoter and regulatory elements for CAR expression. This method used adeno-associated viral (AAV) vectors based on AAV6 to deliver the donor template encoding the CAR construct. Since the original publication, improvements have been made to this targeted CAR integration technique; however, none of those techniques focused on improving the AAV vector used to deliver the therapeutic cargo. The herein presented study developed a novel AAV capsid directed evolution platform that allows for specifically selecting for novel AAV capsid variants that enable more efficient targeted gene editing-mediated CAR construct integration into the TRAC locus in primary T cells. Using this new platform, we selected several novel AAVs that enable more efficient editing in T cells than AAV6. Two novel capsids, AAV-T1 and AAV-T2, were able to mediate 5-fold improvement for on-target knockin, which resulted in 5-fold reduction of the vector dose to produce highly cytolytic T cells against a brain tumor cell line.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2801-2818"},"PeriodicalIF":12.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824321","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}

引用次数: 0

Autologous transplantation of mitochondria/rAAV IGF-I platforms in human osteoarthritic articular chondrocytes to treat osteoarthritis. 线粒体/rAAV IGF-I平台在人骨关节炎关节软骨细胞内的自体移植作为治疗人骨关节炎的新概念

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2024-12-30 DOI: 10.1016/j.ymthe.2024.12.047

Gang Zhong, Wei Liu, Jagadeesh K Venkatesan, Dan Wang, Henning Madry, Magali Cucchiarini

{"title":"Autologous transplantation of mitochondria/rAAV IGF-I platforms in human osteoarthritic articular chondrocytes to treat osteoarthritis.","authors":"Gang Zhong, Wei Liu, Jagadeesh K Venkatesan, Dan Wang, Henning Madry, Magali Cucchiarini","doi":"10.1016/j.ymthe.2024.12.047","DOIUrl":"10.1016/j.ymthe.2024.12.047","url":null,"abstract":"Despite various available treatments, highly prevalent osteoarthritis (OA) cannot be cured in patients. In light of evidence showing mitochondria dysfunction during the disease progression, our goal was to develop a novel therapeutic concept based on the transplantation of mitochondria as a platform to deliver recombinant adeno-associated virus (rAAV) gene vectors with potency for OA. For the first time, to our best knowledge, we report the successful creation of a safe mitochondria/rAAV system effectively promoting the overexpression of a candidate insulin-like growth factor I (IGF-I) by administration to autologous human osteoarthritic articular chondrocytes versus control conditions (reporter mitochondria/rAAV lacZ system, rAAV-free system, absence of mitochondria transplantation; up to 8.4-fold difference). The candidate mitochondria/rAAV IGF-I system significantly improved key activities in the transplanted cells (proliferation/survival, extracellular matrix production, mitochondria functions) relative to the control conditions (up to a 9.5-fold difference), including when provided in a pluronic F127 (PF127) hydrogel for reinforced delivery (up to a 5.9-fold difference). Such effects were accompanied by increased levels of cartilage-specific SOX9 and Mfn-1 (mitochondria fusion) and decreased levels of Drp-1 (mitochondria fission) and proinflammatory tumor necrosis factor alpha (TNF-α; up to 4.5-fold difference). This study shows the potential of combining the use of mitochondria with rAAV as a promising approach for human OA.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2900-2912"},"PeriodicalIF":12.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915307","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}

引用次数: 0

Clinical development of allogeneic chimeric antigen receptor αβ-T cells. 异体嵌合抗原受体αβ-T细胞的临床研究。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub 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":"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":"2426-2440"},"PeriodicalIF":12.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172288/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lung endothelial transduction in a patient that succumbed to acute respiratory distress syndrome following high-dose rAAV9 gene therapy. 高剂量rAAV9基因治疗致急性呼吸窘迫综合征患者的肺内皮转导

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2025-05-28 DOI: 10.1016/j.ymthe.2025.05.017

Juliette Hordeaux, R Jason Lamontagne, Sushobhana Bandyopadhyay, Peter Bell, James M Wilson, Terence R Flotte

引用次数: 0