Gene Therapy最新文献_第7页

Development of an AAV-RNAi strategy to silence the dominant variant GNAO1 c.607G>A linked to encephalopathy 开发一种AAV-RNAi策略来沉默与脑病相关的显性变异gnao1c . 607g >a。

IF 4.5 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy

Pub Date : 2025-04-14 DOI: 10.1038/s41434-025-00532-x

Evgenii A. Lunev, Natalia V. Klementieva, Svetlana G. Vassilieva, Egor A. Volovikov, David Jappy, Irina M. Savchenko, Ekaterina A. Svetlova, Anna V. Polikarpova, Maria Y. Shubina, Danil M. Spirin, Ksenia S. Anufrieva, Petr R. Lebedev, Vladimir M. Pokrovsky, Marina V. Utkina, Viktoriya G. Krut’, Mikhail Sintsov, Sergey Popov, Alexey V. Deykin, Andrei Rozov, Tatiana V. Egorova, Maryana V. Bardina

Heterozygous mutations in GNAO1 cause an ultra-rare neurodevelopmental disease called GNAO1 encephalopathy, characterized by infantile epilepsy and movement disorder. Here, we provide a functional characterization of the hotspot mutation GNAO1 c.607G>A (p.G203R) and conduct early-phase development of an adeno-associated virus (AAV)-mediated gene therapy approach. The GNAO1 gene encodes the Gαo protein that is involved in neuronal signaling. We showed that the Gαo-G203R lost its ability to enhance forskolin-stimulated cAMP synthesis in HEK293T cells. In primary neuronal culture, Gαo-G203R had a dominant-negative effect on neuronal activity and GABAB-dependent synaptic release. To ablate the mutant protein, we used selective silencing of the pathogenic variant using effectors of RNA interference (RNAi). We selected the short hairpin RNA (sh1500) that suppressed the c.607G>A transcripts, resulting in a 3.8-fold increase in the ratio of wild-type to mutant GNAO1 transcripts in patient-specific neurons. We also detected off-target effects of sh1500 as well as transcriptome changes associated with AAV transduction and RNAi activation. We improved the AAV construct by using an artificial miRNA (miR1500) and the neuron-specific hSyn promoter. Systemic administration of AAV9-hSyn-miR1500 did not cause pathological changes in Gnao1-GGA mice with a “humanized” target sequence. Importantly, AAV9 transduced Gαo-positive neurons in the striatum, thalamus, substantia nigra, and cerebellum, which we defined as primary targets for gene therapy. Our findings pave the road toward the development of AAV-RNAi approaches for dominant-negative GNAO1 variants.

GNAO1的杂合突变导致一种称为GNAO1脑病的超罕见神经发育疾病，以婴儿癫痫和运动障碍为特征。在这里，我们提供了热点突变GNAO1 c.607G> a （p.G203R）的功能特征，并进行了腺相关病毒（AAV）介导的基因治疗方法的早期开发。GNAO1基因编码参与神经元信号传导的Gαo蛋白。我们发现Gαo-G203R在HEK293T细胞中失去了增强福斯克林刺激的cAMP合成的能力。在原代神经元培养中，Gαo-G203R对神经元活性和gabab依赖性突触释放具有显性负向影响。为了清除突变蛋白，我们使用RNA干扰效应物（RNAi）选择性沉默致病变异。我们选择了短发夹RNA （sh1500）抑制c.607G>A转录本，导致患者特异性神经元中野生型与突变型GNAO1转录本的比例增加3.8倍。我们还检测到sh1500的脱靶效应以及与AAV转导和RNAi激活相关的转录组变化。我们使用人工miRNA （miR1500）和神经元特异性hSyn启动子来改进AAV结构。在具有“人源化”靶序列的Gnao1-GGA小鼠中，系统给药AAV9-hSyn-miR1500不会引起病理改变。重要的是，AAV9转导了纹状体、丘脑、黑质和小脑中的g αo阳性神经元，我们将其定义为基因治疗的主要靶点。我们的发现为开发针对GNAO1显性阴性变异的AAV-RNAi方法铺平了道路。

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引用次数: 0

Expression of anti-amyloid CARs in microglia promotes efficient and selective phagocytosis of Aβ1‒42 小胶质细胞中抗淀粉样蛋白CARs的表达促进了Aβ1-42的有效和选择性吞噬。

IF 4.5 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy

Pub Date : 2025-04-10 DOI: 10.1038/s41434-025-00534-9

Christina N. Heiss, Rebecca Riise, Eric Hanse, Stefanie Fruhwürth, Henrik Zetterberg, Andreas Björefeldt

Genetic engineering of microglial cells is a promising therapeutic avenue emerging with advancements in gene delivery techniques. Using a recently developed AAV capsid for efficient in vitro transduction we report the engineering of microglia with CARs (CAR-Mic) targeting phagocytosis of amyloid beta 1‒42 (Aβ42). Functional screening of seven CAR constructs in human iPSC-derived microglia revealed up to 6-fold increases in internalized Aβ relative to viral control. CAR-driven phagocytic enhancement was selective for Aβ, dependent on intracellular domain signaling, and was confirmed in primary mouse microglia. These findings highlight the potential of using this approach to target dysfunctional microglia in Alzheimer’s disease and other CNS disorders.

随着基因传递技术的进步，小胶质细胞的基因工程是一种很有前途的治疗途径。利用最近开发的AAV衣壳进行有效的体外转导，我们报道了靶向吞噬淀粉样蛋白β 1-42 （a - β42）的CAR-Mic工程小胶质细胞。在人类ipsc衍生的小胶质细胞中，7种CAR构建体的功能筛选显示，相对于病毒对照，内化的Aβ增加了6倍。car驱动的吞噬增强对Aβ具有选择性，依赖于细胞内信号传导，并在小鼠原代小胶质细胞中得到证实。这些发现强调了使用这种方法靶向阿尔茨海默病和其他中枢神经系统疾病的功能失调小胶质细胞的潜力。

引用次数: 0

Is dystrophin immunogenicity a barrier to advancing gene therapy for Duchenne muscular dystrophy? 肌营养不良蛋白免疫原性是推进杜氏肌营养不良基因治疗的障碍吗？

IF 4.5 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy

Pub Date : 2025-04-03 DOI: 10.1038/s41434-025-00531-y

Dariusz C. Górecki, Pawel Kalinski, Joanna Pomeroy

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to severe disability and premature death in young men. As DMD is caused by the absence of dystrophin, therapeutic development has focused on strategies to restore dystrophin expression. These include readthrough of premature stop codons, exon skipping to restore the reading frame, and gene therapy. The first two methods are mutation-specific, benefiting only subsets of patients, whereas gene therapy could treat all individuals with DMD. Immunogenicity of dystrophin may challenge these efforts. The immune system can recognize dystrophin as a neo-antigen, just as it can recognize newly arising antigens present on mutated cells. An in-depth evaluation of anti-dystrophin immune response as a factor affecting the treatment effectiveness is needed. Key questions include the underlying mechanisms of immunity induction by antigenic epitopes of the re-expressed dystrophin, the impact of such responses on the therapeutic efficacy, and the role of patient-specific risk factors, such as preimmunization due to revertant fibres, chronic muscle inflammation, pre-existing T lymphocytes reactive to dystrophin, which avoided deletion in dystrophic thymus, or antigen cross-reactivity. Patients’ immune status assessment before treatment may help mitigating anti-dystrophin responses. Exploring potential therapeutic strategies to enhance treatment outcomes is also essential: Since DMD can be diagnosed at birth, early dystrophin re-expression could prevent damage and also potentially induce neonatal tolerance. In older patients, carefully managed immunosuppression and tolerogenic protocols could pave the way for more successful dystrophin replacement therapies.

杜氏肌营养不良症（DMD）是一种导致年轻男性严重残疾和过早死亡的神经肌肉疾病。由于DMD是由肌营养不良蛋白缺乏引起的，治疗发展的重点是恢复肌营养不良蛋白表达的策略。这些方法包括读取过早终止密码子，外显子跳跃以恢复阅读框，以及基因治疗。前两种方法是突变特异性的，只对一部分患者有益，而基因疗法可以治疗所有的DMD患者。肌营养不良蛋白的免疫原性可能会挑战这些努力。免疫系统可以识别肌营养不良蛋白作为一种新抗原，就像它可以识别突变细胞上新产生的抗原一样。需要深入评估抗肌营养不良蛋白免疫反应作为影响治疗效果的因素。关键问题包括再表达的肌营养不良蛋白抗原表位诱导免疫的潜在机制，这种反应对治疗效果的影响，以及患者特异性风险因素的作用，如由于纤维逆转而预先免疫，慢性肌肉炎症，预先存在的T淋巴细胞对肌营养不良蛋白反应，避免在营养不良胸腺中缺失，或抗原交叉反应。患者治疗前的免疫状态评估可能有助于减轻抗肌营养不良反应。探索潜在的治疗策略以提高治疗效果也很重要：由于DMD可以在出生时诊断出来，因此早期肌营养不良蛋白的再表达可以预防损伤，也可能诱导新生儿耐受。在老年患者中，精心管理的免疫抑制和耐受性方案可以为更成功的肌营养不良蛋白替代疗法铺平道路。

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引用次数: 0

Early life safety profiling of gene therapy for spinal muscular atrophy. 脊髓性肌萎缩症基因治疗的早期生命安全性分析。

IF 4.6 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy

Pub Date : 2025-04-01 DOI: 10.1038/s41434-025-00529-6

Rebecca G Spellman, Leillani L Ha, Salomé Da Silva Duarte Lepez, Elizabeth A Arruda, Emma Rodrigues, Kathryn J Swoboda, Christiano R R Alves

The present study examines the safety profile of intravenous onasemnogene abeparvovec gene therapy in a real-world setting, both alone or in combination with intrathecal antisense oligonucleotide nusinersen therapy in two cohorts of patients with spinal muscular atrophy (SMA). The first cohort included eight presymptomatic infants treated solely with onasemnogene abeparvovec, while the second cohort comprised six symptomatic infants receiving onasemnogene abeparvovec and nusinersen co-therapy. All patients received the corticosteroid prednisolone coincident with gene therapy. Circulating alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were measured to determine potential hepatoxicity, the primary focus of this study. Elevated ALT and AST levels were observed in one pre-symptomatic and three symptomatic patients post-treatment. However, all values returned to normal levels within 3 months of onasemnogene abeparvovec injection. Nusinersen treatment received previously or coincident with gene therapy did not impact the transient elevation of liver transaminases. This study highlights the importance of early intervention with molecular treatments for SMA and indicates that prior or coincident treatment with nusinersen is unlikely to impact safety of onasemnogene apoparvovec and could theoretically improve clinical outcomes in symptomatic infants or in those with gene therapy delayed beyond the immediate neonatal period.

本研究考察了在现实世界中静脉注射onasemnogene abeparvovec基因治疗的安全性，在两组脊髓性肌萎缩症（SMA）患者中单独或联合鞘内反义寡核苷酸nusinsen治疗。第一个队列包括8名症状前婴儿单独接受onasemnogene abparvovec治疗，而第二个队列包括6名接受onasemnogene abparvovec和nusinersen联合治疗的症状前婴儿。所有患者在接受基因治疗的同时接受皮质类固醇强的松龙治疗。检测循环丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平以确定潜在的肝毒性，这是本研究的主要焦点。1例出现症状前，3例出现症状后，ALT和AST水平升高。然而，所有数值在注射onasemnogene abparvovec后3个月内恢复到正常水平。先前接受Nusinersen治疗或与基因治疗同时接受Nusinersen治疗对肝转氨酶的短暂升高没有影响。该研究强调了早期干预SMA分子治疗的重要性，并表明先前或同时使用nusinersen治疗不太可能影响onasemnogene apparvovec的安全性，理论上可以改善有症状婴儿或延迟到新生儿期之后的基因治疗的临床结果。

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引用次数: 0

Organoids - the future of pre-clinical development of AAV gene therapy for CNS disorders. 类器官- AAV基因治疗中枢神经系统疾病临床前发展的未来。

IF 4.6 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy

Pub Date : 2025-03-27 DOI: 10.1038/s41434-025-00527-8

Vivienne M Kaiser, Anai Gonzalez-Cordero

Advancements in our understanding of genetic disease and adeno-associated virus has prompted great excitement into the field of AAV-mediated gene therapy, particularly for genetic diseases of the central nervous system, including retinal disorders. Despite significant progress, exemplified by the approval of therapies such as Luxturna® and Zolgensma®, a substantial number of therapies remain in pre-clinical or early clinical stages, with many failing to advance to later phases. Whilst the use of animal models to test safety and delivery route efficacy of AAV treatments is imperative, differences in tissue structure and physiology between humans and animal models has restricted precise disease modelling and gene therapy development for many CNS disorders. Alongside the FDA push for non-animal alternative models, researchers are increasingly turning to human-based models, including stem cell-derived organoids, which can offer a more accurate representation of human cellular microenvironments and niches. As such, this review explores the advantages and limitations of brain and retinal organoids as pre-clinical models of disease, with a primary focus on their utility in identifying novel AAV capsids, cell-specific promoters, and their role in recent pre-clinical AAV gene therapy studies.

我们对遗传疾病和腺相关病毒的理解的进步，促使人们对aav介导的基因治疗领域，特别是中枢神经系统的遗传疾病，包括视网膜疾病，产生了极大的兴奋。尽管取得了重大进展，例如Luxturna®和Zolgensma®等疗法的批准，但仍有大量疗法处于临床前或早期临床阶段，许多疗法未能进入后期阶段。虽然使用动物模型来测试AAV治疗的安全性和递送途径有效性是必要的，但人类和动物模型之间的组织结构和生理差异限制了许多中枢神经系统疾病的精确疾病建模和基因治疗的发展。随着FDA推动非动物替代模型，研究人员越来越多地转向基于人类的模型，包括干细胞衍生的类器官，它可以更准确地代表人类细胞微环境和生态位。因此，本综述探讨了脑和视网膜类器官作为疾病临床前模型的优势和局限性，主要关注它们在鉴定新型AAV衣壳、细胞特异性启动子方面的应用，以及它们在最近的临床前AAV基因治疗研究中的作用。

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引用次数: 0

Optimization of adeno-associated viral (AAV) gene therapies vectors for balancing efficacy, longevity and safety for clinical application 腺相关病毒（AAV）基因治疗载体的优化，以平衡临床应用的疗效、寿命和安全性。

IF 4.5 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy

Pub Date : 2025-03-26 DOI: 10.1038/s41434-025-00524-x

Neel Mehta, Rénald Gilbert, Parminder S. Chahal, Maria J. Moreno, Nasha Nassoury, Nathalie Coulombe, Richard Gingras, Alaka Mullick, Simon Drouin, Marc Sasseville, Jyoti Latawa, Krishnaraj Tiwari, Wendy Lin, Emily M. Harvey, Fudan Miao, Colin J. D. Ross, Michael R. Hayden

Adeno-associated viral (AAV) vectors are an ideal platform for gene therapy due to their ability to deliver therapeutic cargos safely and effectively across various target organs. Their low immunogenicity contributes to long-lasting therapeutic effects. However, recent insights highlight the significance of CpG content within AAV vectors, where unmethylated CpG dinucleotides can trigger a TLR9-mediated immune response, leading to the rapid elimination of transduced cells. Clinical evidence indicates an inverse relationship between CpG content and therapeutic success, with lower CpG counts correlating with sustained transgene expression. Here, we sought to optimize a novel, CpG-rich AAV8 vector, referred to as pVR59, designed for treating lipoprotein lipase deficiency (LPLD). We strategically reduced CpG levels in pVR59, resulting in the development of pNC182, a CpG-depleted vector that maintains therapeutic efficacy. A single intramuscular injection of pNC182 demonstrated comparable effectiveness to pVR59 in normalizing lipemia and hypertriglyceridemia in LPLD mouse models, with a 38% reduction in total CpG count. These findings support the clinical application of pNC182 as a safe, long-lasting AAV gene therapy for LPLD and provide a framework for future AAV vector designs aimed at maximizing therapeutic efficacy while minimizing immunogenic responses in human settings.

腺相关病毒（AAV）载体是基因治疗的理想平台，因为它们能够安全有效地在各种靶器官之间传递治疗货物。它们的低免疫原性有助于持久的治疗效果。然而，最近的见解强调了AAV载体中CpG含量的重要性，其中未甲基化的CpG二核苷酸可以触发tlr9介导的免疫反应，导致转导细胞的快速消除。临床证据表明，CpG含量与治疗成功呈反比关系，较低的CpG计数与持续的转基因表达相关。在这里，我们试图优化一种新的，富含cpg的AAV8载体，称为pVR59，设计用于治疗脂蛋白脂肪酶缺乏症（LPLD）。我们战略性地降低了pVR59中的CpG水平，从而开发了pNC182，这是一种保持治疗效果的CpG缺失载体。在LPLD小鼠模型中，单次肌肉注射pNC182在使血脂和高甘油三酯血症正常化方面显示出与pVR59相当的有效性，总CpG计数减少38%。这些发现支持了pNC182作为一种安全、持久的AAV基因治疗LPLD的临床应用，并为未来AAV载体设计提供了框架，旨在最大限度地提高治疗效果，同时减少人类环境中的免疫原性反应。

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引用次数: 0

CRISPR targeting of SNPs associated with age-related macular degeneration in ARPE-19 cells: a potential model for manipulating the complement system CRISPR靶向ARPE-19细胞中与年龄相关性黄斑变性相关的snp：操纵补体系统的潜在模型

IF 4.6 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy

Pub Date : 2025-03-18 DOI: 10.1038/s41434-025-00522-z

Ahmed Salman, Won Kyung Song, Tina Storm, Michelle E. McClements, Robert E. MacLaren

Age-related Macular degeneration (AMD) is a major cause of vision loss and is linked to several predisposing single nucleotide polymorphisms (SNPs). CRISPR-mediated genome editing offers the potential to target negatively associated SNPs in an allele-specific manner, necessitating the need for a relevant cell model. The ARPE-19 cell line, with its stable monolayer growth and retinal pigment epithelium (RPE) characteristics, serves as an ideal model for AMD studies. Chronic inflammation and complement system dysregulation are implicated in AMD pathogenesis. Most genetic variations associated with AMD are in complement genes, suggesting their regulatory role. In this study, we conducted targeted PCRs to identify AMD-related SNPs in ARPE-19 cells and used CRISPR constructs to assess allele-specific activity. Guide RNA sequences were cloned into an EF-1-driven SpCas9 vector and packaged into lentivirus. Targeting efficiencies were evaluated with TIDE analysis, and allele-specificity was measured with NGS analysis 30 days post-transduction. Our results showed varying targeting efficiencies depending on guide RNA efficacy. For example, TIDE analysis of CFH SNPs rs1061170 and rs1410996 revealed efficiencies of 35.5% and 33.8%, respectively. CFB SNP rs4541862 showed efficiencies from 3% to 36.7%, and rs641153 ranged from 3.4% to 23.8%. Additionally, allele-specific targeting of AMD-related SNPs rs1061170, rs1410996, rs4541862, and rs641153 ranged from 48% to 52% in heterozygous differentiated ARPE-19 cells. These findings demonstrate the potential to manipulate the complement system in an AMD model by targeting disease-associated SNPs in an allele-specific manner, offering a promising therapeutic approach.

年龄相关性黄斑变性（AMD）是视力丧失的主要原因，与几种易感的单核苷酸多态性（snp）有关。crispr介导的基因组编辑提供了以等位基因特异性方式靶向负相关snp的潜力，因此需要相关的细胞模型。ARPE-19细胞系具有稳定的单层生长和视网膜色素上皮（RPE）特性，是AMD研究的理想模型。慢性炎症和补体系统失调与AMD的发病有关。大多数与AMD相关的遗传变异都在补体基因中，表明它们具有调节作用。在本研究中，我们在ARPE-19细胞中进行了靶向pcr鉴定amd相关snp，并使用CRISPR构建物评估等位基因特异性活性。将引导RNA序列克隆到ef -1驱动的SpCas9载体中，并包装到慢病毒中。用TIDE分析评估靶向效率，并在转导后30天用NGS分析测量等位基因特异性。我们的结果显示不同的靶向效率取决于向导RNA的功效。例如，CFH snp rs1061170和rs1410996的TIDE分析效率分别为35.5%和33.8%。CFB SNP rs4541862的效率范围为3% ~ 36.7%，rs641153的效率范围为3.4% ~ 23.8%。此外，在杂合分化的ARPE-19细胞中，amd相关snp rs1061170、rs1410996、rs4541862和rs641153的等位基因特异性靶向范围从48%到52%不等。这些发现表明，通过以等位基因特异性的方式靶向疾病相关的snp，可以在AMD模型中操纵补体系统，提供了一种有希望的治疗方法。

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引用次数: 0

AAV-based gene replacement therapy prevents and halts manifestation of abnormal neurological phenotypes in a novel mouse model of PMM2-CDG 在一种新型PMM2-CDG小鼠模型中，基于aav的基因替代疗法可以预防和停止异常神经表型的表现。

IF 4.5 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy

Pub Date : 2025-03-17 DOI: 10.1038/s41434-025-00525-w

Mian-ling Zhong, Kent Lai

Inherited Phosphomannomutase 2 (PMM2) deficiency, also known as PMM2-CDG, is the most prevalent N-linked congenital disorder of glycosylation (CDG), occurring in approximately 1 in 20,000 individuals in certain populations. Patients exhibit a spectrum of symptoms, with neurological involvement being a prominent feature, often manifesting as the initial clinical sign, and can range from isolated neurological deficits to severe multi-organ dysfunction. Given the absence of curative treatments and a high mortality rate before the age of two, alongside considerable lifelong morbidity, there is an urgent need for innovative therapeutic approaches. To address this unmet need, we developed a tamoxifen-inducible Pmm2 knockout (KO) mouse model with widespread tissue deficiency of Pmm2 expression. Characterization of the mouse model to-date revealed distinct neurological phenotypes relevant to PMM2-CDG, as assessed by the Composite Phenotype Scoring System and Open Field Test. Notably, PMM2 augmentation through AAV9-PMM2 gene replacement therapy prevented and halted the disease-relevant neurological phenotypes induced by Pmm2 KO in the animals. These findings underscored the promise of AAV9-PMM2 gene replacement in managing PMM2-CDG.

遗传性磷酸腺苷交换酶2 （PMM2）缺乏症，也称为PMM2-CDG，是最常见的n -连锁先天性糖基化（CDG）疾病，在某些人群中发病率约为2万分之一。患者表现出一系列症状，神经系统受累是一个突出特征，通常表现为最初的临床体征，范围从孤立的神经功能缺损到严重的多器官功能障碍。鉴于缺乏治疗方法，两岁以下儿童死亡率高，加上终生发病率高，迫切需要创新的治疗方法。为了解决这一未满足的需求，我们开发了一种他莫昔芬诱导的Pmm2敲除（KO）小鼠模型，该模型具有广泛的Pmm2组织表达缺陷。迄今为止，通过复合表型评分系统和开放场测试，小鼠模型的表征显示了与PMM2-CDG相关的不同神经表型。值得注意的是，通过AAV9-PMM2基因替代疗法增加PMM2可以预防和停止动物中PMM2 KO诱导的疾病相关神经表型。这些发现强调了AAV9-PMM2基因替代治疗PMM2-CDG的前景。

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引用次数: 0

AAV vector engineering for human aorta transduction: becoming a smooth operator AAV载体工程用于人主动脉转导：成为一个平滑算子。

IF 4.5 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy

Pub Date : 2025-03-17 DOI: 10.1038/s41434-025-00526-9

Kleopatra Rapti, Dirk Grimm

引用次数: 0

Improved induction of ribozyme-controlled AAV transgene via peptide-conjugated morpholino oligos 利用肽偶联寡核苷酸改进诱导核酶控制的AAV转基因。

IF 4.6 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy

Pub Date : 2025-02-26 DOI: 10.1038/s41434-025-00520-1

Tianyi Cheng, Baohui Chen, Wei Zou

引用次数: 0