Molecular Therapy最新文献_第9页

Bispecific receptor decoys: A new player to a crowded field 双特异性受体诱饵：一个进入拥挤区域的新玩家

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-21 DOI: 10.1016/j.ymthe.2025.06.015

Glenn Yiu

引用次数: 0

Retraction Notice to: LncRNA ODRUL Contributes to Osteosarcoma Progression through the miR-3182/MMP2 Axis. 撤回通知：LncRNA ODRUL通过miR-3182/MMP2轴促进骨肉瘤进展。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-19 DOI: 10.1016/j.ymthe.2025.06.030

Kun-Peng Zhu, Xiao-Long Ma, Chun-Lin Zhang

引用次数: 0

Effective Use of BCMA-Targeting Bispecific T-Cell-Engaging Antibody in Treatment Refractory LRP4-positive Myasthenia Gravis. 靶向bcma的双特异性t细胞结合抗体在治疗难治性lrp4阳性重症肌无力中的有效应用

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-17 DOI: 10.1016/j.ymthe.2025.06.029

Stefanie Schreiber,Marwa Al-Dubai,Stefan Vielhaber,Lora Lefterova,Sascha Dietrich,Tobias Ruck,Sven Meuth,Denise Walther,Dimitrios Mougiakakos

{"title":"Effective Use of BCMA-Targeting Bispecific T-Cell-Engaging Antibody in Treatment Refractory LRP4-positive Myasthenia Gravis.","authors":"Stefanie Schreiber,Marwa Al-Dubai,Stefan Vielhaber,Lora Lefterova,Sascha Dietrich,Tobias Ruck,Sven Meuth,Denise Walther,Dimitrios Mougiakakos","doi":"10.1016/j.ymthe.2025.06.029","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.029","url":null,"abstract":"Myasthenia gravis (MG) is an antibody-mediated autoimmune disease affecting the neuromuscular junction. Refractory MG, particularly in cases associated with rare anti-LRP4 antibodies, presents significant treatment challenges. Teclistamab, a bispecific antibody targeting BCMA and CD3, redirects T cells against plasma cells and is approved for multiple myeloma treatment. Increasing interest surrounds the use of T-cell-based therapies in B-cell-mediated autoimmune diseases, particularly CAR T cells, which have demonstrated efficacy in achieving deep B-cell depletion and durable remissions. Additionally, emerging data support the use of T cell engagers (TCEs) as an alternative strategy for targeting autoreactive B cells. We report the case of a 47-year-old woman with severe, refractory, LRP4-positive MG. Despite multiple treatments, she remained severely affected, wheelchair-bound, and experiencing significant disability. Off-label teclistamab administration resulted in mild cytokine release syndrome (CRS), self-resolving lymphopenia, and hypogammaglobulinemia. Residual circulating B cells were eliminated, anti-LRP4 antibodies became undetectable, and clinical scores improved significantly. The patient regained mobility and has sustained remission during short-term follow-up. This case highlights the therapeutic potential of teclistamab and BCMA-targeting strategies in MG, warranting further investigation.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"44 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320095","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

CRISPR for Cystic Fibrosis: advances and insights from a systematic review. CRISPR治疗囊性纤维化：来自系统综述的进展和见解。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-17 DOI: 10.1016/j.ymthe.2025.06.021

Lucia Nicosia,Patrick T Harrison

{"title":"CRISPR for Cystic Fibrosis: advances and insights from a systematic review.","authors":"Lucia Nicosia,Patrick T Harrison","doi":"10.1016/j.ymthe.2025.06.021","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.021","url":null,"abstract":"Cystic Fibrosis (CF) is a severe genetic disorder caused by loss-of-function mutations in the CFTR gene. Gene editing approaches have the potential to correct such mutations. This systematic review outlines the mechanisms of the main CRISPR-based technologies, and, through cross-study comparisons, analyzes twenty-seven research articles that applied these technologies to target CF-causing variants. We report and discuss the strategy design, target cell selection, editing efficiency, prevalence of editing byproducts and levels of CFTR functional restoration achieved in each work, with the aim of providing technical insights for further exploration of CRISPR-based gene editing approaches. Our findings show that the F508del and W1282X mutations were the most extensively studied CF-causing variants, though over fifteen mutations were targeted overall. The majority of works under review explored the use of homology-directed repair (HDR) or base editing, with a growing number reporting efficient prime editing. Some studies tackled multiple individual mutations, compared different editors, or tested strategies across various models, while others focused on approaches that rescue CFTR function without directly correcting a mutation. Several works also proposed strategies that could address multiple variants with a single approach, while others highlighted technical difficulties in editing certain regions of the CFTR gene. This cross-study comparison also emphasizes the need for standardized reporting of editing efficiency and functional rescue, and stresses the importance of further single-cell RNA sequencing and in-vivo studies to reach clinically-relevant conclusions. However, as gene editing techniques continue to evolve, and with over sixty ongoing CRISPR-based clinical trials, there is growing optimism for meaningful advancements in CF gene-editing therapeutics.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"89 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320097","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 with covalently-closed-end AAV vector for Spinal Muscular Atrophy. 共价闭端AAV载体基因治疗脊髓性肌萎缩症。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-14 DOI: 10.1016/j.ymthe.2025.06.028

Haolin Duan,Ciliu Zhang,Zhongliang Zhang,Xiaole Wang,Junping Zhang,Lifen Yang,Fang He,Leilei Mao,Li Yang,Zou Pan,Renzhi Han,Weiming Wang,Dao Pan,Fei Yin,Weidong Xiao,Jing Peng

{"title":"Gene Therapy with covalently-closed-end AAV vector for Spinal Muscular Atrophy.","authors":"Haolin Duan,Ciliu Zhang,Zhongliang Zhang,Xiaole Wang,Junping Zhang,Lifen Yang,Fang He,Leilei Mao,Li Yang,Zou Pan,Renzhi Han,Weiming Wang,Dao Pan,Fei Yin,Weidong Xiao,Jing Peng","doi":"10.1016/j.ymthe.2025.06.028","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.028","url":null,"abstract":"Covalently closed-end adeno-associated virus vector (cceAAV) is a new generation of self-complementary vector (scAAV) which does not utilize a mutant ITR for vector production. Importantly, packaged genomes of these cceAAV vectors are markedly more intact than traditional scAAVs, which typically contain a large fraction of incomplete genomes, including many that lost their self-complementary configuration. Here, we report first-in-human experience with a cceAAV vector. High quality clinical grade cceAAV vector based on AAV9 produced in 200 liters of suspension 293 cells with a total yield of 4.3 × 1016 vector genomes (vg). Clinical trial in two spinal muscular atrophy (SMA) patients via intravenous injection at 12-24 months of age revealed no treatment-associated severe adverse events with a dose ranging from 6 × 1013 vg/kg to 1.2 × 1014 vg/kg. Both patients showed rapid improvements in motor capabilities after gene therapy, as evidenced by substantial gains in motor function and electrophysiological parameters and capacity for independent mobility. Our strategy enabled us to perform gene therapy in older SMA patients who had received initial treatment with RNA-splicing modifying drug during infancy. These early data provide preliminary evidence for clinical use of cceAAV vectors, though further validation in larger cohorts is warranted.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"12 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295808","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

Blood Phenylalanine lowering partially reverses white matter changes in a mouse model of Phenylketonuria. 苯丙酮尿小鼠模型中血液苯丙氨酸降低部分逆转白质变化。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-14 DOI: 10.1016/j.ymthe.2025.06.020

Rachna Manek,Weixiao Huang,Yinyin Huang,Lilu Guo,Cathleen S Cornell,Mohammed Salman Shazeeb,Alexander Verbitsky,Robert Jackson,Jennifer Johnson,Patricia Berthelette,Dan Yu,Edith L Pfister,Dinesh Bangari,Xiaoyou Ying,Dinesh Kumar,Christian Mueller,Sirkka Kyostio-Moore

{"title":"Blood Phenylalanine lowering partially reverses white matter changes in a mouse model of Phenylketonuria.","authors":"Rachna Manek,Weixiao Huang,Yinyin Huang,Lilu Guo,Cathleen S Cornell,Mohammed Salman Shazeeb,Alexander Verbitsky,Robert Jackson,Jennifer Johnson,Patricia Berthelette,Dan Yu,Edith L Pfister,Dinesh Bangari,Xiaoyou Ying,Dinesh Kumar,Christian Mueller,Sirkka Kyostio-Moore","doi":"10.1016/j.ymthe.2025.06.020","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.020","url":null,"abstract":"Phenylketonuria (PKU) is a genetic defect caused by lack of liver enzyme phenylalanine hydroxylase (PAH). This deficiency results in elevated blood Phenylalanine (Phe) levels and neurotoxicity which is manifested by reduced brain size, lower neurotransmitter levels, and reduced myelination. The goal of this study was to investigate brain myelination defects and their reversibility upon blood Phe lowering by analyzing the corpus callosum (CC) of adult Pahenu2 (PAH-deficient) mice. MRI and immunostaining demonstrated a significant reduction in CC volume in Pahenu2 mice. Treatment with an adeno-associated vector (AAV) encoding mouse PAH for 3.5 months improved but did not completely normalize CC volume. Total cholesterol, a major component of myelin, was unchanged in the CC of Pahenu2 mouse while some sterol intermediates were significantly reduced by treatment. Single nuclei transcriptomics showed upregulation of oxidative stress-related pathways, and increased expression of transthyretin, ApoE, Cst3, and Cd81 in CC in Pahenu2 mice. Normalization of blood Phe restored gene expression to levels comparable to heterozygous mice and was associated with generation of differentiated myelin-producing oligodendrocyte subtypes and neuroprotective astrocytes. In summary, Pahenu2 mice showed white matter abnormalities and changes in transcriptome and sterol profiles, which were partially corrected by normalization of blood Phe.","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":"144295868","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

AAV9-Mediated Gene Supplementation Therapy prevents and Rescues Arrhythmogenic Cardiomyopathy in Pnpla2-mutated Mice. aav9介导的基因补充疗法预防和拯救pnpla2突变小鼠的心律失常性心肌病

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-14 DOI: 10.1016/j.ymthe.2025.06.023

Xiulin Zhang,Congrui Wang,Yuan Chang,Hao Jia,Yue Zhang,Yifan Wang,Weiteng Wang,Han Han,Yuhong Hu,Xijia Shao,Shuang Wen,Siyu Tan,Ningning Zhang,Xiumeng Hua,Hao Cui,Xiao Chen,Jiangping Song

{"title":"AAV9-Mediated Gene Supplementation Therapy prevents and Rescues Arrhythmogenic Cardiomyopathy in Pnpla2-mutated Mice.","authors":"Xiulin Zhang,Congrui Wang,Yuan Chang,Hao Jia,Yue Zhang,Yifan Wang,Weiteng Wang,Han Han,Yuhong Hu,Xijia Shao,Shuang Wen,Siyu Tan,Ningning Zhang,Xiumeng Hua,Hao Cui,Xiao Chen,Jiangping Song","doi":"10.1016/j.ymthe.2025.06.023","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.023","url":null,"abstract":"Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder involving ventricular arrhythmias, cardiac dysfunction, and fibrofatty myocardial replacement. Current treatments are largely palliative, with heart transplantation as the only definitive option for advanced ACM. Here we show that, building upon our previous identification of a patient with a PNPLA2c.G245A/c.G245A mutation, we developed a murine model carrying the same mutation, faithfully mimicking key ACM phenotypes such as arrhythmias, lipid accumulation, and fibrosis. Using an adeno-associated virus 9 (AAV9) vector to deliver the human PNPLA2 gene, we demonstrated that early intervention prevented ACM onset, while later treatment reversed established symptoms and extended survival. Treated mice exhibited improved cardiac function, lipid metabolism, and normalized fatty acid pathways, verified by single-nucleus sequencing. These findings highlight the promise of AAV9-mediated PNPLA2 gene supplementation as an effective therapeutic strategy for ACM, supporting further clinical exploration.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"6 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295866","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

AAV-mediated gene therapy for focal epilepsy by expressing neuropeptide Y and Y2 receptor in rodent and non-human primate hippocampus. aav介导的基因治疗局灶性癫痫通过表达神经肽Y和Y2受体在啮齿动物和非人灵长类动物海马。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-14 DOI: 10.1016/j.ymthe.2025.06.019

Barbara Terzic,Esbjörn Melin,Pernilla Fagergren,David Dobry,Stefano Cattaneo,Iris Giupponi,Barbara Bettegazzi,Michele Simonato,Karin Agerman,Merab Kokaia,Lawrence Moon,Elizabeth Ramsburg

{"title":"AAV-mediated gene therapy for focal epilepsy by expressing neuropeptide Y and Y2 receptor in rodent and non-human primate hippocampus.","authors":"Barbara Terzic,Esbjörn Melin,Pernilla Fagergren,David Dobry,Stefano Cattaneo,Iris Giupponi,Barbara Bettegazzi,Michele Simonato,Karin Agerman,Merab Kokaia,Lawrence Moon,Elizabeth Ramsburg","doi":"10.1016/j.ymthe.2025.06.019","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.019","url":null,"abstract":"Epilepsy affects approximately 50 million people worldwide, and over 30% of patients are considered treatment-resistant to currently available anti-seizure drugs. Neuropeptide Y (NPY) has been shown to inhibit excitatory synaptic transmission in hippocampal slices from human epilepsy patients via Y2 receptors (Y2R), and overexpression of NPY and/or Y2R in the hippocampus reduces seizures in rodent models of epilepsy. In this study, we demonstrate that AAV-mediated delivery of NPY and Y2R using a novel vector (SPK100.NPY-Y2R) inhibits seizures in rodents. SPK100.NPY-Y2R reduced spontaneous neuronal activity in primary rat cortical cultures and attenuated evoked neuronal activity in ex vivo slices of mouse hippocampus. Furthermore, intrahippocampal administration of SPK100.NPY-Y2R reduced the progression and duration of seizures in a rat model of rapid kindling. Parallel experiments confirmed that hippocampal overexpression of NPY and Y2R is also sufficient to reduce spontaneous seizures in a genetic mouse model of epilepsy (synapsin triple knockout). We also demonstrated successful magnetic resonance-guided, convection enhanced delivery of SPK100.NPY-Y2R to the hippocampus of Papio hamadryas (baboon). This approach achieved favorable vector biodistribution and transduction in the hippocampus, with no observed adverse events. These findings support the development of an intrahippocampal AAV.NPY-Y2R therapy for treating seizures in patients with temporal lobe epilepsy.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"42 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295869","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

RNA-DNA hybrid binding domain broadens the editing window of base editors. RNA-DNA杂交结合域拓宽了碱基编辑器的编辑窗口。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-06-14 DOI: 10.1016/j.ymthe.2025.06.024

Yue Yang,Zihao Fu,Shengcheng Deng,Guanglan Wu,Chuanle Wang,Xiao Luo,Rui Kang,Yuxi Chen,Chengxiang Peng,Pengfei Zhang,Kaixin Cui,Fen Wan,Junhua Wang,Qin Zhou,Wei Chen,Yuanyan Xiong,Wenbin Ma,Zhou Songyang,Puping Liang

{"title":"RNA-DNA hybrid binding domain broadens the editing window of base editors.","authors":"Yue Yang,Zihao Fu,Shengcheng Deng,Guanglan Wu,Chuanle Wang,Xiao Luo,Rui Kang,Yuxi Chen,Chengxiang Peng,Pengfei Zhang,Kaixin Cui,Fen Wan,Junhua Wang,Qin Zhou,Wei Chen,Yuanyan Xiong,Wenbin Ma,Zhou Songyang,Puping Liang","doi":"10.1016/j.ymthe.2025.06.024","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.024","url":null,"abstract":"Adenine base editors (ABEs) and cytosine base editors (CBEs) are prominent tools for precise genome editing but are hindered by limited editing activity at positions proximal to the protospacer adjacent motif (PAM). This study investigates the potential of enhancing base editors editing activity by fusing them with RNA-DNA hybrid binding domains (RHBDs). Specifically, fusing ABE8e with the RHBD of Homo sapiens RNaseH1 (RHBD1) significantly increased A-to-G editing efficiency in the PAM-proximal region (A9-A15) by up to 3.5-fold, while reducing off-target cytosine editing. Additionally, RHBD1 is compatible with ABEmax, BE4max, and dual base editor (eA&C-BEmax), enhancing their editing activity at the PAM-proximal bases. Notably, RHBD1-fused BE4max led to a 3.1-fold improvement in C-to-T editing efficiency at PAM-proximal region (C9-C12). Furthermore, we demonstrated that RHBD1-fused ABE8e could effectively edit disease-related single nucleotide variations (SNVs) in human cells, and validated its efficacy in adult mouse liver. These findings highlight the significance of the RHBD in expanding editing window and the applicability of base editors for gene therapy and disease modeling.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"10 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295867","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

Neonatal systemic gene therapy restores cardiorespiratory function in a rat model of Pompe disease. 新生儿全身基因治疗可恢复庞贝病大鼠模型的心肺功能。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-14 DOI: 10.1016/j.ymthe.2025.06.022

David D Fuller, Sabhya Rana, Prajwal P Thakre, Ethan S Benevides, Megan K Pope, Adrian G Todd, Victoria N Jensen, Lauren Vaught, Denise A Cloutier, Roberto A Ribas, Reece C Larson, Matthew S Gentry, Ramon C Sun, Vijay Chandran, Manuela Corti, Darin J Falk, Barry J Byrne

{"title":"Neonatal systemic gene therapy restores cardiorespiratory function in a rat model of Pompe disease.","authors":"David D Fuller, Sabhya Rana, Prajwal P Thakre, Ethan S Benevides, Megan K Pope, Adrian G Todd, Victoria N Jensen, Lauren Vaught, Denise A Cloutier, Roberto A Ribas, Reece C Larson, Matthew S Gentry, Ramon C Sun, Vijay Chandran, Manuela Corti, Darin J Falk, Barry J Byrne","doi":"10.1016/j.ymthe.2025.06.022","DOIUrl":"10.1016/j.ymthe.2025.06.022","url":null,"abstract":"Absence of functional acid-α-glucosidase (GAA) leads to early onset Pompe disease with cardiorespiratory and neuromuscular failure. A novel Pompe rat model (Gaa-/-) was used to test the hypothesis that neonatal gene therapy with adeno-associated virus serotype 9 (AAV9) restores cardiorespiratory neuromuscular function across the lifespan. Temporal vein administration of AAV9-DES-GAA or sham (saline) injection was done on postnatal day 1; rats were studied at 6-12 months old. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI) revealed that AAV-GAA treatment normalized diaphragm muscle glycogen as well as glycans. In vivo magnetic resonance imaging demonstrated that impaired cardiac volumes in Gaa-/- rats were corrected by AAV-GAA treatment. Biochemical assays showed that AAV treatment increased GAA activity in the heart, diaphragm, quadriceps, and spinal cord. Inspiratory tidal volume and minute ventilation were increased in AAV-GAA-treated vs. saline-treated Pompe rats. Neurophysiological phrenic nerve recordings and spinal histological evaluation indicated that AAV-GAA treatment drove functional neuronal GAA expression. We conclude that neonatal AAV9-DES-GAA therapy drives sustained, functional GAA expression and improved cardiorespiratory function in the Gaa-/- rat model of Pompe disease.","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":"144302567","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