Gene Therapy最新文献_第8页

A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis 在创伤后骨关节炎大型动物模型中确定 scAAVIL-1ra 最佳剂量的试验研究。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-09-11 DOI: 10.1038/s41434-023-00420-2

P. Thampi, K. A. Seabaugh, L. M. Pezzanite, C. R. Chu, J. N. Phillips, J. C. Grieger, C. W. McIlwraith, R. J. Samulski, L. R. Goodrich

{"title":"A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis","authors":"P. Thampi, K. A. Seabaugh, L. M. Pezzanite, C. R. Chu, J. N. Phillips, J. C. Grieger, C. W. McIlwraith, R. J. Samulski, L. R. Goodrich","doi":"10.1038/s41434-023-00420-2","DOIUrl":"10.1038/s41434-023-00420-2","url":null,"abstract":"Gene therapy approaches using adeno-associated viral vectors have been successfully tested in the equine post-traumatic osteoarthritis (PTOA) model. Owing to differences in the levels of transgene expression and adverse tissue reactions observed in published studies, we sought to identify a safe therapeutic dose of scAAVIL-1ra in an inflamed and injured joint that would result in improved functional outcomes without any adverse events. scAAVIL-1ra was delivered intra-articularly over a 100-fold range, and horses were evaluated throughout and at the end of the 10-week study. A dose-related increase in IL-1ra levels with a decrease in PGE2 levels was observed, with the peak IL-1ra concentration being observed 7 days post-treatment in all groups. Perivascular infiltration with mononuclear cells was observed within the synovial membrane of the joint treated with the highest viral dose of 5 × 1012 vg, but this was absent in the lower-dosed joints. The second-highest dose of scAAVeqIL-1ra 5 × 1011 vg demonstrated elevated IL-1ra levels without any cellular response in the synovium. Taken together, the data suggest that the 10-fold lower dose of 5 × 1011vg scAAVIL-1ra would be a safe therapeutic dose in an equine model of PTOA.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10727982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10216073","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}

引用次数: 0

Selection of appropriate non-clinical animal models to ensure translatability of novel AAV-gene therapies to the clinic 选择适当的非临床动物模型，以确保新型 AAV 基因疗法可转化为临床疗法。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-08-23 DOI: 10.1038/s41434-023-00417-x

Mark Singh, Andrew Brooks, Parto Toofan, Keith McLuckie

引用次数: 0

Safety and biodistribution of XC001 (encoberminogene rezmadenovec) gene therapy in rats: a potential therapy for cardiovascular diseases XC001（encoberminogene rezmadenovec）基因疗法在大鼠体内的安全性和生物分布：心血管疾病的一种潜在疗法。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-08-18 DOI: 10.1038/s41434-023-00416-y

Duncan J. Stewart, Albert Gianchetti, Dawn Byrnes, Howard C. Dittrich, Barb Thorne, Linda L. Manza, Rickey R. Reinhardt

{"title":"Safety and biodistribution of XC001 (encoberminogene rezmadenovec) gene therapy in rats: a potential therapy for cardiovascular diseases","authors":"Duncan J. Stewart, Albert Gianchetti, Dawn Byrnes, Howard C. Dittrich, Barb Thorne, Linda L. Manza, Rickey R. Reinhardt","doi":"10.1038/s41434-023-00416-y","DOIUrl":"10.1038/s41434-023-00416-y","url":null,"abstract":"Adenovirus-mediated gene therapy holds promise for the treatment of cardiovascular diseases such as refractory angina. However, potential concerns around immunogenicity and vector dissemination from the target injected tissue require evaluation. This study was undertaken to evaluate the safety and biodistribution of XC001, a replication-deficient adenovirus serotype 5 vector expressing multiple isoforms of human vascular endothelial growth factor (VEGF), following direct administration into normal rat myocardium. Animals received the buffer formulation or increasing doses of XC001 (1 × 107, 2.5 × 108 or 2.5 × 109 viral particles). Based on in-life parameters (general health, body weights, clinical pathology, serum cardiac troponin I, plasma VEGF, and gross necropsy), there were no findings of clinical concern. On Day 8, intramyocardial administration of XC001 was associated with dose-related, left ventricular myocardial inflammation at injection sites, resolving by Day 30. XC001 DNA was not detected in blood at any time but was present at Day 8 around the site of injection and to a much lesser extent in the spleen, liver, and lungs, persisting at low levels in the heart and spleen until at least Day 91. These findings demonstrate that intramyocardial injection of XC001 is supported for use in human studies.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-023-00416-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012194","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}

引用次数: 0

Preclinical safety and biodistribution of CRISPR targeting SIV in non-human primates 以 SIV 为靶标的 CRISPR 在非人灵长类动物中的临床前安全性和生物分布。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-08-17 DOI: 10.1038/s41434-023-00410-4

Tricia H. Burdo, Chen Chen, Rafal Kaminski, Ilker K. Sariyer, Pietro Mancuso, Martina Donadoni, Mandy D. Smith, Rahsan Sariyer, Maurizio Caocci, Shuren Liao, Hong Liu, Wenwen Huo, Huaqing Zhao, John Misamore, Mark G. Lewis, Vahan Simonyan, Elaine E. Thompson, Ethan Y. Xu, Thomas J. Cradick, Jennifer Gordon, Kamel Khalili

{"title":"Preclinical safety and biodistribution of CRISPR targeting SIV in non-human primates","authors":"Tricia H. Burdo, Chen Chen, Rafal Kaminski, Ilker K. Sariyer, Pietro Mancuso, Martina Donadoni, Mandy D. Smith, Rahsan Sariyer, Maurizio Caocci, Shuren Liao, Hong Liu, Wenwen Huo, Huaqing Zhao, John Misamore, Mark G. Lewis, Vahan Simonyan, Elaine E. Thompson, Ethan Y. Xu, Thomas J. Cradick, Jennifer Gordon, Kamel Khalili","doi":"10.1038/s41434-023-00410-4","DOIUrl":"10.1038/s41434-023-00410-4","url":null,"abstract":"In this study, we demonstrate the safety and utility of CRISPR-Cas9 gene editing technology for in vivo editing of proviral DNA in ART-treated, virally controlled simian immunodeficiency virus (SIV) infected rhesus macaques, an established model for HIV infection. EBT-001 is an AAV9-based vector delivering SaCas9 and dual guide RNAs designed to target multiple regions of the SIV genome: the viral LTRs, and the Gag gene. The results presented here demonstrate that a single IV inoculation of EBT-001 at each of 3 dose levels (1.4 × 1012, 1.4 × 1013 and 1.4 × 1014 genome copies/kg) resulted in broad and functional biodistribution of AAV9-EBT-001 to known tissue reservoirs of SIV. No off-target effects or abnormal pathology were observed, and animals returned to their normal body weight after receiving EBT-001. Importantly, the macaques that received the 2 highest doses of EBT-001 showed improved absolute lymphocyte counts as compared to antiretroviral-treated controls. Taken together, these results demonstrate safety, biodistribution, and in vivo proviral DNA editing following IV administration of EBT-001, supporting the further development of CRISPR-based gene editing as a potential therapeutic approach for HIV in humans.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-023-00410-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10014588","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}

引用次数: 0

Biodistribution of lentiviral transduced adipose-derived stem cells for “ex-vivo” regional gene therapy for bone repair 慢病毒转导脂肪干细胞的生物分布，用于骨修复的 "体外 "区域基因治疗。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-08-11 DOI: 10.1038/s41434-023-00415-z

Jennifer A. Bell, Kevin Collon, Cory Mayfield, Matthew C. Gallo, Stephanie W. Chang, Osamu Sugiyama, Amy H. Tang, Roger Hollis, Shefali Chopra, Donald B. Kohn, Jay R. Lieberman

{"title":"Biodistribution of lentiviral transduced adipose-derived stem cells for “ex-vivo” regional gene therapy for bone repair","authors":"Jennifer A. Bell, Kevin Collon, Cory Mayfield, Matthew C. Gallo, Stephanie W. Chang, Osamu Sugiyama, Amy H. Tang, Roger Hollis, Shefali Chopra, Donald B. Kohn, Jay R. Lieberman","doi":"10.1038/s41434-023-00415-z","DOIUrl":"10.1038/s41434-023-00415-z","url":null,"abstract":"Ex-vivo gene therapy has been shown to be an effective method for treating bone defects in pre-clinical models. As gene therapy is explored as a potential treatment option in humans, an assessment of the safety profile becomes an important next step. The purpose of this study was to evaluate the biodistribution of viral particles at the defect site and various internal organs in a rat femoral defect model after implantation of human ASCs transduced with lentivirus (LV) with two-step transcriptional activation (TSTA) of bone morphogenetic protein-2 (LV-TSTA-BMP-2). Animals were sacrificed at 4-, 14-, 56-, and 84-days post implantation. The defects were treated with either a standard dose (SD) of 5 million cells or a high dose (HD) of 15 million cells to simulate a supratherapeutic dose. Treatment groups included (1) SD LV-TSTA-BMP-2 (2) HD LV-TSTA-BMP-2, (3) SD LV-TSTA-GFP (4) HD LV-TSTA-GFP and (5) SD nontransduced cells. The viral load at the defect site and ten organs was assessed at each timepoint. Histology of all organs, ipsilateral tibia, and femur were evaluated at each timepoint. There were nearly undetectable levels of LV-TSTA-BMP-2 transduced cells at the defect site at 84-days and no pathologic changes in any organ at all timepoints. In conclusion, human ASCs transduced with a lentiviral vector were both safe and effective in treating critical size bone defects in a pre-clinical model. These results suggest that regional gene therapy using lentiviral vector to treat bone defects has the potential to be a safe and effective treatment in humans.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9982682","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}

引用次数: 0

Targeted shock-and-kill HIV-1 gene therapy approach combining CRISPR activation, suicide gene tBid and retargeted adenovirus delivery 结合 CRISPR 激活、自杀基因 tBid 和再靶向腺病毒递送的靶向冲击-杀伤 HIV-1 基因疗法。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-08-09 DOI: 10.1038/s41434-023-00413-1

Sarah Klinnert, Corinne D. Schenkel, Patrick C. Freitag, Huldrych F. Günthard, Andreas Plückthun, Karin J. Metzner

{"title":"Targeted shock-and-kill HIV-1 gene therapy approach combining CRISPR activation, suicide gene tBid and retargeted adenovirus delivery","authors":"Sarah Klinnert, Corinne D. Schenkel, Patrick C. Freitag, Huldrych F. Günthard, Andreas Plückthun, Karin J. Metzner","doi":"10.1038/s41434-023-00413-1","DOIUrl":"10.1038/s41434-023-00413-1","url":null,"abstract":"Infections with the human immunodeficiency virus type 1 (HIV-1) are incurable due the long-lasting, latent viral reservoir. The shock-and-kill cure approach aims to activate latent proviruses in HIV-1 infected cells and subsequently kill these cells with strategies such as therapeutic vaccines or immune enhancement. Here, we combined the dCas9-VPR CRISPR activation (CRISPRa) system with gRNA-V, the truncated Bid (tBid)-based suicide gene strategy and CD3-retargeted adenovirus (Ad) delivery vectors, in an all-in-one targeted shock-and-kill gene therapy approach to achieve specific elimination of latently HIV-1 infected cells. Simultaneous transduction of latently HIV-1 infected J-Lat 10.6 cells with a CD3-retargeted Ad-CRISPRa-V and Ad-tBid led to a 57.7 ± 17.0% reduction of productively HIV-1 infected cells and 2.4-fold ± 0.25 increase in cell death. The effective activation of latent HIV-1 provirus by Ad-CRISPRa-V was similar to the activation control TNF-α. The strictly HIV-1 dependent and non-leaky killing by tBid could be demonstrated. Furthermore, the high transduction efficiencies of up to 70.8 ± 0.4% by the CD3-retargeting technology in HIV-1 latently infected cell lines was the basis of successful shock-and-kill. This novel targeted shock-and-kill all-in-one gene therapy approach has the potential to safely and effectively eliminate HIV-1 infected cells in a highly HIV-1 and T cell specific manner.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-023-00413-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10320531","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}

引用次数: 0

CRISPR/sgRNA-directed synergistic activation mediator (SAM) as a therapeutic tool for Parkinson´s disease CRISPR/sgRNA定向协同激活介质（SAM）作为帕金森病的治疗工具。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-08-04 DOI: 10.1038/s41434-023-00414-0

Luis Fernando Narváez-Pérez, Francisco Paz-Bermúdez, José Arturo Avalos-Fuentes, Aurelio Campos-Romo, Benjamín Florán-Garduño, José Segovia

{"title":"CRISPR/sgRNA-directed synergistic activation mediator (SAM) as a therapeutic tool for Parkinson´s disease","authors":"Luis Fernando Narváez-Pérez, Francisco Paz-Bermúdez, José Arturo Avalos-Fuentes, Aurelio Campos-Romo, Benjamín Florán-Garduño, José Segovia","doi":"10.1038/s41434-023-00414-0","DOIUrl":"10.1038/s41434-023-00414-0","url":null,"abstract":"Parkinson`s disease (PD) is the second most prevalent neurodegenerative disease, and different gene therapy strategies have been used as experimental treatments. As a proof-of-concept for the treatment of PD, we used SAM, a CRISPR gene activation system, to activate the endogenous tyrosine hydroxylase gene (th) of astrocytes to produce dopamine (DA) in the striatum of 6-OHDA-lesioned rats. Potential sgRNAs within the rat th promoter region were tested, and the expression of the Th protein was determined in the C6 glial cell line. Employing pseudo-lentivirus, the SAM complex and the selected sgRNA were transferred into cultures of rat astrocytes, and gene expression and Th protein synthesis were ascertained; furthermore, DA release into the culture medium was determined by HPLC. The DA-producing astrocytes were implanted into the striatum of 6-OHDA hemiparkinsonian rats. We observed motor behavior improvement in the lesioned rats that received DA-astrocytes compared to lesioned rats receiving astrocytes that did not produce DA. Our data indicate that the SAM-induced expression of the astrocyte´s endogenous th gene can generate DA-producing astrocytes that effectively reduce the motor asymmetry induced by the lesion.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-023-00414-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9930854","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}

引用次数: 0

Sildenafil increases AAV9 transduction after a systemic administration and enhances AAV9-dystrophin therapeutic effect in mdx mice 西地那非可增加全身给药后的 AAV9 转导，并增强 AAV9-dystrophin 对 mdx 小鼠的治疗效果。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-07-27 DOI: 10.1038/s41434-023-00411-3

Kaiyi Zhou, Meng Yuan, Jiabao Sun, Feixu Zhang, Xiaoying Zong, Zhanao Li, Dingyue Tang, Lichen Zhou, Jing Zheng, Xiao Xiao, Xia Wu

{"title":"Sildenafil increases AAV9 transduction after a systemic administration and enhances AAV9-dystrophin therapeutic effect in mdx mice","authors":"Kaiyi Zhou, Meng Yuan, Jiabao Sun, Feixu Zhang, Xiaoying Zong, Zhanao Li, Dingyue Tang, Lichen Zhou, Jing Zheng, Xiao Xiao, Xia Wu","doi":"10.1038/s41434-023-00411-3","DOIUrl":"10.1038/s41434-023-00411-3","url":null,"abstract":"Adeno-associated virus (AAV) vectors have been successfully used to deliver genes for treating rare diseases. However, the systemic administration of high AAV vector doses triggers several adverse effects, including immune response, the asymptomatic elevation of liver transaminase levels, and complement activation. Thus, improving AAV transduction and reducing AAV dosage for treatment is necessary. Recently, we found that a phosphodiesterase-5 inhibitor significantly promoted AAV9 transduction in vitro by regulating the caveolae and macropinocytosis pathways. When AAV9-Gaussian luciferase (AAV9-Gluc) and AAV9-green fluorescent protein (AAV9-GFP) were injected intravenously into mice pre-treated with sildenafil, the expressions of Gluc in the plasma and GFP in muscle tissues significantly increased (P < 0.05). Sildenafil also improved Evans blue permeation in tissues. Additionally, we found that sildenafil promoted Treg proliferation, inhibited B-cell activation, and decreased anti-AAV9 IgG levels (P < 0.05). Furthermore, sildenafil significantly promoted Duchenne muscular dystrophy gene therapy efficacy using AAV9 in mdx mice; it increased micro-dystrophin gene expression, forelimb grip strength, and time spent on the rotarod test, decreased serum creatine kinase levels, and ameliorated histopathology by improving muscle cell morphology and reducing fibrosis (P < 0.05). These results show that sildenafil significantly improved AAV transduction, suppressed the levels of anti-AAV9 IgG, and enhanced the efficacy of gene therapy.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10259421","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}

引用次数: 0

Correction: Site-specific modifications to AAV8 capsid yields enhanced brain transduction in the neonatal MPS IIIB mouse 更正：对AAV8衣壳的位点特异性修饰增强了新生MPS IIIB小鼠的脑转导。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-07-27 DOI: 10.1038/s41434-023-00412-2

Janine A. Gilkes, Benjamin L. Judkins, Brontie N. Herrera, Ronald J. Mandel, Sanford L. Boye, Shannon E. Boye, Arun Srivastava, Coy D. Heldermon

引用次数: 0

Immunobiology of a rationally-designed AAV2 capsid following intravitreal delivery in mice 小鼠玻璃体内给药后合理设计的AAV2衣壳的免疫生物学。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-06-29 DOI: 10.1038/s41434-023-00409-x

Michael Whitehead, Andrew Sage, Tom Burgoyne, Andrew Osborne, Patrick Yu-Wai-Man, Keith R. Martin

{"title":"Immunobiology of a rationally-designed AAV2 capsid following intravitreal delivery in mice","authors":"Michael Whitehead, Andrew Sage, Tom Burgoyne, Andrew Osborne, Patrick Yu-Wai-Man, Keith R. Martin","doi":"10.1038/s41434-023-00409-x","DOIUrl":"10.1038/s41434-023-00409-x","url":null,"abstract":"Adeno-associated virus serotype 2 (AAV2) is a viral vector that can be used to deliver therapeutic genes to diseased cells in the retina. One strategy for altering AAV2 vectors involves the mutation of phosphodegron residues, which are thought to be phosphorylated/ubiquitinated in the cytosol, facilitating degradation of the vector and the inhibition of transduction. As such, mutation of phosphodegron residues have been correlated with increased transduction of target cells, however, an assessment of the immunobiology of wild-type and phosphodegron mutant AAV2 vectors following intravitreal (IVT) delivery to immunocompetent animals is lacking in the current literature. In this study, we show that IVT of a triple phosphodegron mutant AAV2 capsid is associated with higher levels of humoral immune activation, infiltration of CD4 and CD8 T-cells into the retina, generation of splenic germinal centre reactions, activation of conventional dendritic cell subsets, and elevated retinal gliosis compared to wild-type AAV2 capsids. However, we did not detect significant changes in electroretinography arising after vector administration. We also demonstrate that the triple AAV2 mutant capsid is less susceptible to neutralisation by soluble heparan sulphate and anti-AAV2 neutralising antibodies, highlighting a possible utility for the vector in terms of circumventing pre-existing humoral immunity. In summary, the present study highlights novel aspects of rationally-designed vector immunobiology, which may be relevant to their application in preclinical and clinical settings.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10352016","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}

引用次数: 0