Human gene therapy最新文献

{"title":"Pre-Existing Immunity to a Nucleic Acid Contaminant-Derived Antigen Mediates Transaminitis and Resultant Diminished Transgene Expression in a Mouse Model of Hepatic Recombinant Adeno-Associated Virus-Mediated Gene Transfer.","authors":"Mark A Brimble, Christopher L Morton, Stephen M Winston, Isaiah L Reeves, Yunyu Spence, Pei-Hsin Cheng, Junfang Zhou, Amit C Nathwani, Paul G Thomas, Aisha Souquette, Andrew M Davidoff","doi":"10.1089/hum.2023.188","DOIUrl":"10.1089/hum.2023.188","url":null,"abstract":"<p><p>Liver injury with concomitant loss of therapeutic transgene expression can be a clinical sequela of systemic administration of recombinant adeno-associated virus (rAAV) when used for gene therapy, and a significant barrier to treatment efficacy. Despite this, it has been difficult to replicate this phenotype in preclinical models, thereby limiting the field's ability to systematically investigate underlying biological mechanisms and develop interventions. Prior animal models have focused on capsid and transgene-related immunogenicity, but the impact of concurrently present nontransgene or vector antigens on therapeutic efficacy, such as those derived from contaminating nucleic acids within rAAV preps, has yet to be investigated. In this study, using Ad5-CMV_GFP-immunized immunocompetent BALB/cJ mice, and a coagulation factor VIII expressing rAAV preparation that contains green flourescent protein (GFP) cDNA packaged as P5-associated contaminants, we establish a model to induce transaminitis and observe concomitant therapeutic efficacy reduction after rAAV administration. We observed strong epitope-specific anti-GFP responses in splenic CD8+ T cells when GFP cDNA was delivered as a P5-associated contaminant of rAAV, which coincided and correlated with alanine and aspartate aminotransferase elevations. Furthermore, we report a significant reduction in detectable circulating FVIII protein, as compared with control mice. Lastly, we observed an elevation in the detection of AAV8 capsid-specific T cells when GFP was delivered either as a contaminant or transgene to Ad5-CMV_GFP-immunized mice. We present this model as a potential tool to study the underlying biology of post-AAV hepatotoxicity and demonstrate the potential for T cell responses against proteins produced from AAV encapsidated nontherapeutic nucleic acids, to interfere with efficacious gene transfer.</p>","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"477-489"},"PeriodicalIF":3.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of FoxP3⁺ Regulatory T Cells in Modulating Immune Responses to Adeno-Associated Virus Gene Therapy.","authors":"Maite Muñoz-Melero, Moanaro Biswas","doi":"10.1089/hum.2023.227","DOIUrl":"10.1089/hum.2023.227","url":null,"abstract":"<p><p>Adeno-associated virus (AAV) gene therapy is making rapid strides owing to its wide range of therapeutic applications. However, development of serious immune responses to the capsid antigen or the therapeutic transgene product hinders its full clinical impact. Immune suppressive (IS) drug treatments have been used in various clinical trials to prevent the deleterious effects of cytotoxic T cells to the viral vector or transgene, although there is no consensus on the best treatment regimen, dosage, or schedule. Regulatory T cells (Tregs) are crucial for maintaining tolerance against self or nonself antigens. Of importance, Tregs also play an important role in dampening immune responses to AAV gene therapy, including tolerance induction to the transgene product. Approaches to harness the tolerogenic effect of Tregs include the use of selective IS drugs that expand existing Tregs, and skew activated conventional T cells into antigen-specific peripherally induced Tregs. In addition, Tregs can be expanded <i>ex vivo</i> and delivered as cellular therapy. Furthermore, receptor engineering can be used to increase the potency and specificity of Tregs allowing for suppression at lower doses and reducing the risk of disrupting protective immunity. Because immune-mediated toxicities to AAV vectors are a concern in the clinic, strategies that can enhance or preserve Treg function should be considered to improve both the safety and efficacy of AAV gene therapy.</p>","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"439-450"},"PeriodicalIF":3.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pfizer Weighs Next Steps after DMD Therapy Linked to Boy's Death Fails Phase III Trial.","authors":"Alex Philippidis","doi":"10.1089/hum.2024.38567.bfs","DOIUrl":"10.1089/hum.2024.38567.bfs","url":null,"abstract":"","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":"35 13-14","pages":"413-415"},"PeriodicalIF":3.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Enzyme-Linked Immunosorbent Spot Assay for the Assessment of Adeno-Associated Virus Peptides to Examine Immune Safety.","authors":"Sara Rose Krivoshik, Lindsey Dzielak, April R Masters, Jennifer Hall, Alison J Johnson","doi":"10.1089/hum.2023.180","DOIUrl":"10.1089/hum.2023.180","url":null,"abstract":"<p><p>Adeno-associated virus (AAV)-based gene therapies have shown promise as novel treatments for rare genetic disorders such as hemophilia A and spinal muscular atrophy. However, cellular immune responses mediated by cytotoxic (CD8⁺) and helper (CD4⁺) T cells may target vector-transduced cells as well as healthy immune cells, impacting safety and efficacy. In this study, we describe the optimization and reproducibility of interferon-γ (IFNγ)-based and interleukin-2 (IL-2)-based enzyme-linked immunosorbent spot (ELISpot) assays for measuring T cell responses against AAV peptide antigens. For method optimization, peripheral blood mononuclear cells (PBMCs) were isolated from healthy human donors and stimulated with commercially available major histocompatibility complex (MHC) class I or II-specific peptides as positive controls. Peptide pools were designed from published AAV8 and AAV9 capsid protein sequences and then used to assess the presence of AAV-specific T cell responses. Our results demonstrate a measurable increase in IFNγ and IL-2-producing cells after AAV peptide presentation. Furthermore, there was an observed difference in the magnitude and specificity of response to peptide pools based on AAV serotype and donor. Finally, using individual peptides, we identified a region of the AAV9 capsid protein that can elicit an immunogenic response. This work shows the applicability of ELISpot in assessing anti-AAV immune responses and provides insight into how novel recombinant AAV vectors could be designed to reduce immunogenic potential.</p>","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"506-516"},"PeriodicalIF":3.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate Immune Sensing of Adeno-Associated Virus Vectors.","authors":"Di Cao, Barry J Byrne, Ype P de Jong, Cox Terhorst, Dongsheng Duan, Roland W Herzog, Sandeep R P Kumar","doi":"10.1089/hum.2024.040","DOIUrl":"10.1089/hum.2024.040","url":null,"abstract":"<p><p>Adeno-associated virus (AAV) based viral vectors are widely used in human gene therapy and form the basis of approved treatments for several genetic diseases. Immune responses to vector and transgene products, however, substantially complicate these applications in clinical practice. The role of innate immune recognition of AAV vectors was initially unclear, given that inflammatory responses early after vector administration were typically mild in animal models. However, more recent research continues to identify innate immune pathways that are triggered by AAV vectors and that serve to provide activation signals for antigen-presenting cells and initiation of adaptive immune responses. Sensing of the AAV genome by the endosomal DNA receptor toll-like receptor 9 (TLR9) promotes early inflammatory response and interferon expression. Thus, activation of the TLR9>MyD88 pathway in plasmacytoid dendritic cells (pDCs) leads to the conditioning of antigen cross-presenting DCs through type I interferon (IFN-I) and ultimately CD8⁺ T cell activation. Alternatively, pDCs may also promote CD8⁺ T cell responses in a TLR9-independent manner by the production of IL-1 cytokines, thereby activating the IL-1R1>MyD88 signaling pathway. AAV can induce cytokine expression in monocyte-derived DCs, which in turn increases antibody formation. Binding of AAV capsid to complement components likely further elevates B cell activation. At high systemic vector doses in humans and in non-human primates, AAV vectors can trigger complement activation, with contributions by classical and alternative pathways, leading to severe toxicities. Finally, evidence for activation of TLR2 by the capsid and of additional innate receptors for nucleic acids has been presented. These observations show that AAV vectors can initiate several and likely redundant innate immune pathways resulting in an exaggerated adaptive immune response.</p>","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"451-463"},"PeriodicalIF":3.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circumventing B Cell Responses to Allow for Redosing of Adeno-Associated Virus Vectors.","authors":"Hildegund C J Ertl","doi":"10.1089/hum.2023.162","DOIUrl":"10.1089/hum.2023.162","url":null,"abstract":"<p><p>Adeno-associated virus (AAV)-mediated gene therapy has made significant progress in the last few decades. Nevertheless, challenges imposed by the immune system remain. The very high doses of AAV vectors used for some disorders have resulted in serious adverse events (SAEs) or even deaths, demonstrating that AAV vector doses that can safely be injected into patients are limited and for some indications below the therapeutic dose. Currently used immunosuppressive drugs have not prevented the SAEs, indicating that it may be prudent to treat patients with repeated transfer of moderate doses rather than a single injection of high doses of AAV vectors. The former approach has been avoided as AAV vectors elicit neutralizing antibodies that prevent successful reapplication of serologically crossreactive vectors. Immunosuppressive regimens that block B cell responses to AAV vectors or treatments that remove AAV neutralizing antibodies thus need to be developed to allow for a shift from toxic single-dose injections of AAV vectors to repeated treatments with more moderate and safe doses. Preventing or blocking antibody responses would also allow for redosing of patients with declining transgene product expression, or for effective AAV-mediated gene transfer into patients with the pre-existing neutralizing antibodies.</p>","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"416-424"},"PeriodicalIF":3.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49676979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of the Cost-Effectiveness Evidence for FDA-Approved Cell and Gene Therapies.","authors":"Sumaya Abuloha, Shu Niu, Darlene Adirika, Benjamin P Harvey, Mikael Svensson","doi":"10.1089/hum.2023.186","DOIUrl":"10.1089/hum.2023.186","url":null,"abstract":"<p><p>Cell and gene therapy (CGT) innovations have provided several significant breakthroughs in recent years. However, CGTs often come with a high upfront cost, raising questions about patient access, affordability, and long-term value. This study reviewed cost-effectiveness analysis (CEA) studies that have attempted to assess the long-term value of Food and Drug Administration (FDA)-approved CGTs. Two reviewers independently searched the Tufts Medical Center CEA Registry to identify all studies for FDA-approved CGTs, per January 2023. A data extraction template was used to summarize the evidence in terms of the incremental cost-effectiveness ratio expressed as the cost per quality-adjusted life year (QALY) and essential modeling assumptions, combined with a template to extract the adherence to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. The review identified 26 CEA studies for seven CGTs. Around half of the base-case cost-effectiveness results indicated that the cost per QALY was below $100,000-$150,000, often used as a threshold for reasonable cost-effectiveness in the United States. However, the results varied substantially across studies for the same treatment, ranging from being considered very cost-effective to far from cost-effective. Most models were based on data from single-arm trials with relatively short follow-ups, and different long-term extrapolations between studies caused large differences in the modeled cost-effectiveness results. In sum, this review showed that, despite the high upfront costs, many CGTs have cost-effectiveness evidence that can support long-term value. Nonetheless, substantial uncertainty regarding long-term value exists because so much of the modeling results are driven by uncertain extrapolations beyond the clinical trial data.</p>","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"365-373"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-Cas Genome Editing in <i>Ex Vivo</i> Human Lungs to Rewire the Translational Path of Genome-Targeting Therapeutics.","authors":"Kumi Mesaki, Haruchika Yamamoto, Stephen Juvet, Jonathan Yeung, Zehong Guan, Akhi Akhter, Yan Yao, Cameron Dickie, Henna Mangat, Aizhou Wang, Gavin W Wilson, Andrea Mariscal, Jim Hu, Alan R Davidson, Benjamin P Kleinstiver, Marcelo Cypel, Mingyao Liu, Shaf Keshavjee","doi":"10.1089/hum.2023.223","DOIUrl":"10.1089/hum.2023.223","url":null,"abstract":"<p><p>The ongoing advancements in CRISPR-Cas technologies can significantly accelerate the preclinical development of both <i>in vivo</i> and <i>ex vivo</i> organ genome-editing therapeutics. One of the promising applications is to genetically modify donor organs prior to implantation. The implantation of optimized donor organs with long-lasting immunomodulatory capacity holds promise for reducing the need for lifelong potent whole-body immunosuppression in recipients. However, assessing genome-targeting interventions in a clinically relevant manner prior to clinical trials remains a major challenge owing to the limited modalities available. This study introduces a novel platform for testing genome editing in human lungs <i>ex vivo</i>, effectively simulating preimplantation genetic engineering of donor organs. We identified gene regulatory elements whose disruption via Cas nucleases led to the upregulation of the immunomodulatory gene interleukin 10 (<i>IL-10)</i>. We combined this approach with adenoviral vector-mediated <i>IL-10</i> delivery to create favorable kinetics for early (immediate postimplantation) graft immunomodulation. Using <i>ex vivo</i> organ machine perfusion and precision-cut tissue slice technology, we demonstrated the feasibility of evaluating CRISPR genome editing in human lungs. To overcome the assessment limitations in <i>ex vivo</i> perfused human organs, we conducted an <i>in vivo</i> rodent study and demonstrated both early gene induction and sustained editing of the lung. Collectively, our findings lay the groundwork for a first-in-human-organ study to overcome the current translational barriers of genome-targeting therapeutics.</p>","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"374-387"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kallistatin Improves High-Fat-Induced Insulin Resistance via Epididymal Adipose Tissue-Derived Exosomes.","authors":"Zi-Wei Yang, Jing-Jing Ji, Yu Jiang, Ya Wu, Jia-Qi Guo, Gen-Shan Ma, Yu-Yu Yao","doi":"10.1089/hum.2023.079","DOIUrl":"10.1089/hum.2023.079","url":null,"abstract":"<p><p><b><i>Objective:</i></b> Studies have found that high expression of human Kallistatin (HKS) in adipose tissue can improve obesity and its associated comorbidities, but the underlying mechanism of specific regulation is unclear. <b><i>Methods:</i></b> An obesity model was built by injecting 8-week-old C57BL/6 mice (<i>n</i> = 6 mice per group) with (Ad.Null and (Ad.HKS adenovirus into epididymal adipose tissue and fed with a high-fat diet (HFD). Insulin resistance-related proteins, AKT and IRS1, were detected in the liver, subcutaneous fat, and skeletal muscle by western blotting after one month of HFD. Epididymal adipose tissue was isolated after 24 h for culture, and exosomes were extracted by differential centrifugation. Enzyme-linked immunosorbent assay detected the expression of HKS protein in serum and exosomes. To examine the role of exosomes in AML12 insulin resistance, we used epididymal adipose tissue-derived exosomes or transfected (Ad.HKS into mature 3T3L1-derived exosomes to interfere with palmitic acid (PA)-induced mouse AML12 insulin resistance model. GW4869 was used to inhibit exosome biogenesis and release. <b><i>Results:</i></b> Our results showed that HFD-induced mice with high expression of HKS in epididymal adipose tissue had slower weight gain, lower serum triglycerides, reduced free fatty acids, and improved liver insulin resistance compared with the (Ad.Null group. We also demonstrated that HKS was enriched in epididymal adipose tissue-derived exosomes and released through the exosome pathway. In PA-induced AML12 cells, insulin resistance was alleviated after incubation of the HKS-related exosome; this effect was reversed with GW4869. <b><i>Conclusion:</i></b> High expression of HKS in epididymal adipose tissue could lead to its exocrine secretion in the form of exosomes and improve liver insulin resistance by promoting the phosphorylation of AKT. Production of high HKS vesicles might be a possible way to alleviate insulin resistance associated with obesity.</p>","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"388-400"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9942957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological Validation of Sedimentation Velocity Analytical Ultracentrifugation Method for Adeno-Associated Virus and Collaborative Calibration of System Suitability Substance.","authors":"Xi Qin, Qikun Yu, Xiang Li, Wei Jiang, Xinchang Shi, Wenxiu Hou, Da Zhang, Zhenzhen Cai, Hua Bi, Wenhong Fan, Youxue Ding, Yichen Yang, Biao Dong, Long Chen, Dehua Huo, Cong Wang, Yong Zhou, Dening Pei, Miao Ye, Chenggang Liang","doi":"10.1089/hum.2023.169","DOIUrl":"10.1089/hum.2023.169","url":null,"abstract":"<p><p>Currently, adeno-associated virus (AAV) is one of the primary gene delivery vectors in gene therapy, facilitating long-term <i>in vivo</i> gene expression. Despite being imperative, it is incredibly challenging to precisely assess AAV particle distribution according to the sedimentation coefficient and identify impurities related to capsid structures. This study performed the systematic methodological validation of quantifying the AAV empty and full capsid ratio. This includes specificity, accuracy, precision, linearity, and parameter variables involving the sedimentation velocity analytical ultracentrifugation (SV-AUC) method. Specifically, SV-AUC differentiated among the empty, partial, full, and high sedimentation coefficient substance (HSCS) AAV particles while evaluating their sedimentation heterogeneity. The intermediate precision analysis of HE (high percentage of empty capsid) and HF (high percentage of full capsid) samples revealed that the specific species percentage, such as empty or full, was more significant than 50%. Moreover, the relative standard deviation (RSD) could be within 5%. Even for empty or partially less than 15%, the RSD could be within 10%. The accuracy recovery rates of empty capsid were between 103.9% and 108.7% across three different mixtures. When the measured percentage of specific species was more significant than 14%, the recovery rate was between 77.9% and 106.6%. Linearity analysis revealed an excellent linear correlation between the empty, partial, and full in the HE samples. The AAV samples with as low as 7.4 × 10¹¹ cp/mL AAV could be accurately quantified with SV-AUC. The parameter variable analyses revealed that variations in cell alignment significantly affected the overall results. Still, the detection wavelength of 235 nm slightly influenced the empty, partial, and full percentages. Minor detection wavelength changes showed no impact on the sedimentation coefficient of these species. However, the temperature affected the measured sedimentation coefficient. These results validated the SV-AUC method to quantify AAV. This study provides solutions to AAV empty and full capsid ratio quantification challenges and the subsequent basis for calibrating the AAV empty capsid system suitability substance. Because of the AAV structure and potential variability complexity in detection, we jointly calibrated empty capsid system suitability substance with three laboratories to accurately detect the quantitative AAV empty and full capsid ratio. The empty capsid system suitability substance could be used as an external reference to measure the performance of the instrument. The results could be compared with multiple QC (quality control) laboratories based on the AAV vector and calibration accuracy. This is crucial for AUC to be used for QC release and promote gene therapy research worldwide.</p>","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"401-411"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}