Gene Therapy最新文献_第5页

Retraction Note: Oncolysis of pancreatic tumour cells by a γ34.5-deleted HSV-1 does not rely upon Ras-activation, but on the PI 3-kinase pathway 撤稿说明：删除了γ34.5的HSV-1对胰腺肿瘤细胞的肿瘤溶解不依赖于Ras激活，而是依赖于PI 3-激酶途径。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-08-16 DOI: 10.1038/s41434-024-00478-6

F. Sarinella, A. Calistri, P. Sette, G. Palù, C. Parolin

引用次数: 0

Correction: Alternative oxidase encoded by sequence-optimized and chemically-modified RNA transfected into mammalian cells is catalytically active 更正：转染到哺乳动物细胞中的经过序列优化和化学修饰的 RNA 所编码的替代氧化酶具有催化活性。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-08-15 DOI: 10.1038/s41434-024-00473-x

Luca Giordano, Manish K. Aneja, Natascha Sommer, Nasim Alebrahimdehkordi, Alireza Seraji, Norbert Weissmann, Carsten Rudolph, Christian Plank, Howard T. Jacobs, Marten Szibor

引用次数: 0

Efficacy of an AAV vector encoding a thermostable form of glucocerebrosidase in alleviating symptoms in a Gaucher disease mouse model 编码恒温型葡萄糖脑苷脂酶的 AAV 载体在减轻戈谢病小鼠模型症状方面的功效

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-08-15 DOI: 10.1038/s41434-024-00476-8

Ivan Milenkovic, Shani Blumenreich, Ariel Hochfelder, Aviya Azulay, Inbal E. Biton, Mirie Zerbib, Roni Oren, Michael Tsoory, Tammar Joseph, Sarel J. Fleishman, Anthony H. Futerman

{"title":"Efficacy of an AAV vector encoding a thermostable form of glucocerebrosidase in alleviating symptoms in a Gaucher disease mouse model","authors":"Ivan Milenkovic, Shani Blumenreich, Ariel Hochfelder, Aviya Azulay, Inbal E. Biton, Mirie Zerbib, Roni Oren, Michael Tsoory, Tammar Joseph, Sarel J. Fleishman, Anthony H. Futerman","doi":"10.1038/s41434-024-00476-8","DOIUrl":"10.1038/s41434-024-00476-8","url":null,"abstract":"Almost all attempts to date at gene therapy approaches for monogenetic disease have used the amino acid sequences of the natural protein. In the current study, we use a designed, thermostable form of glucocerebrosidase (GCase), the enzyme defective in Gaucher disease (GD), to attempt to alleviate neurological symptoms in a GD mouse that models type 3 disease, i.e. the chronic neuronopathic juvenile subtype. Upon injection of an AAVrh10 (adeno-associated virus, serotype rh10) vector containing the designed GCase (dGCase) into the left lateral ventricle of Gba−/−;Gbatg mice, a significant improvement in body weight and life-span was observed, compared to injection of the same mouse with the wild type enzyme (wtGCase). Moreover, a reduction in levels of glucosylceramide (GlcCer), and an increase in levels of GCase activity were seen in the right hemisphere of Gba−/−;Gbatg mice, concomitantly with a significant improvement in motor function, reduction of neuroinflammation and a reduction in mRNA levels of various genes shown previously to be elevated in the brain of mouse models of neurological forms of GD. Together, these data pave the way for the possible use of modified proteins in gene therapy for lysosomal storage diseases and other monogenetic disorders.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 9-10","pages":"439-444"},"PeriodicalIF":4.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00476-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987784","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

The AAV2.7m8 capsid packages a higher degree of heterogeneous vector genomes than AAV2 与 AAV2 相比，AAV2.7m8 的包囊包装异质载体基因组的程度更高。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-08-12 DOI: 10.1038/s41434-024-00477-7

Mengtian Cui, Qin Su, Mitchell Yip, Jackson McGowan, Claudio Punzo, Guangping Gao, Phillip W. L. Tai

{"title":"The AAV2.7m8 capsid packages a higher degree of heterogeneous vector genomes than AAV2","authors":"Mengtian Cui, Qin Su, Mitchell Yip, Jackson McGowan, Claudio Punzo, Guangping Gao, Phillip W. L. Tai","doi":"10.1038/s41434-024-00477-7","DOIUrl":"10.1038/s41434-024-00477-7","url":null,"abstract":"Recombinant adeno-associated virus (rAAV) vectors are currently the only proven vehicles for treating ophthalmological diseases through gene therapy. A wide range of gene therapy programs that target ocular diseases are currently being pursued. Nearly 20 years of research have gone into enhancing the efficacy of targeting retinal tissues and improving transgene delivery to specific cell types. The engineered AAV capsid, AAV2.7m8 is currently among the best capsids for transducing the retina following intravitreal (IVT) injection. However, adverse effects, including intraocular inflammation, have been reported following retinal administration of AAV2.7m8 vectors in clinical trials. Furthermore, we have consistently observed that AAV2.7m8 exhibits low packaging titers irrespective of the vector construct design. In this report, we found that AAV2.7m8 packages vector genomes with a higher degree of heterogeneity than AAV2. We also found that genome-loaded AAV2.7m8 stimulated the infiltration of microglia in mouse retinas following IVT administration, while the response to genome-loaded AAV2 and empty AAV2.7m8 capsids produced much milder responses. This finding suggests that IVT administration of AAV2.7m8 vectors may stimulate retinal immune responses in part because of its penchant to package and deliver non-unit length genomes.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 9-10","pages":"489-498"},"PeriodicalIF":4.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00477-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970988","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

Correction: Andrew C. G. Porter (1955–2023) 更正：安德鲁-波特（1955-2023）。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-08-07 DOI: 10.1038/s41434-024-00474-w

Rafael J. Yáñez-Muñoz, Jane E. Itzhaki

引用次数: 0

Correction: Limited potential of AAV-mediated gene therapy in transducing human mesenchymal stem cells for bone repair applications 更正：AAV 介导的基因疗法在转导人类间充质干细胞用于骨修复方面的潜力有限。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-08-01 DOI: 10.1038/s41434-024-00472-y

Sofia Bougioukli, Morgan Chateau, Heidy Morales, Venus Vakhshori, Osamu Sugiyama, Daniel Oakes, Donald Longjohn, Paula Cannon, Jay R. Lieberman

引用次数: 0

Andrew C. G. Porter (1955–2023) 安德鲁-波特（Andrew C. G. Porter，1955-2023 年）。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-07-29 DOI: 10.1038/s41434-024-00470-0

Rafael J. Yáñez-Muñoz, Jane E. Itzhaki

引用次数: 0

Preclinical evaluation of tissue-selective gene therapies for congenital generalised lipodystrophy 先天性全身性脂肪营养不良的组织选择性基因疗法的临床前评估

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-07-28 DOI: 10.1038/s41434-024-00471-z

Mansi Tiwari, Ahlima Roumane, Nadine Sommer, Weiping Han, Mirela Delibegović, Justin J. Rochford, George D. Mcilroy

{"title":"Preclinical evaluation of tissue-selective gene therapies for congenital generalised lipodystrophy","authors":"Mansi Tiwari, Ahlima Roumane, Nadine Sommer, Weiping Han, Mirela Delibegović, Justin J. Rochford, George D. Mcilroy","doi":"10.1038/s41434-024-00471-z","DOIUrl":"10.1038/s41434-024-00471-z","url":null,"abstract":"Lipodystrophy is a rare disorder which can be life-threatening. Here individuals fail to develop or maintain appropriate adipose tissue stores. This typically causes severe metabolic complications, including hepatic steatosis and lipoatrophic diabetes. There is no cure for lipodystrophy, and treatment options remain very limited. Here we evaluate whether tissue-selective adeno-associated virus (AAV) vectors can provide a targeted form of gene therapy for lipodystrophy, using a preclinical lipodystrophic mouse model of Bscl2 deficiency. We designed AAV vectors containing the mini/aP2 or thyroxine-binding globulin promoter to selectively target adipose or liver respectively. The AAV-aP2 vectors also contained the liver-specific microRNA-122 target sequence, restricting hepatic transgene expression. Systemic delivery of AAV-aP2 vectors overexpressing human BSCL2 restored adipose tissue development and metabolic health in lipodystrophic mice without detectable expression in the liver. High doses (1 × 1012 GCs) of liver-selective vectors led to off target expression and adipose tissue development, whilst low doses (1 × 1010 GCs) expressed selectively and robustly in the liver but did not improve metabolic health. This reveals that adipose tissue-selective, but not liver directed, AAV-mediated gene therapy is sufficient to substantially recover metabolic health in generalised lipodystrophy. This provides an exciting potential new avenue for an effective, targeted, and thereby safer therapeutic intervention.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 9-10","pages":"445-454"},"PeriodicalIF":4.6,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00471-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141785508","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

Amelioration of airway and GI disease in G551D-CF ferrets by AAV1 and AAV6 用 AAV1 和 AAV6 改善 G551D-CF 雪貂的气道和消化道疾病

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-07-28 DOI: 10.1038/s41434-024-00469-7

Cristian Ciobanu, Murali Yanda, Adi Zeidan, Jessica Izzi, William B. Guggino, Liudmila Cebotaru

{"title":"Amelioration of airway and GI disease in G551D-CF ferrets by AAV1 and AAV6","authors":"Cristian Ciobanu, Murali Yanda, Adi Zeidan, Jessica Izzi, William B. Guggino, Liudmila Cebotaru","doi":"10.1038/s41434-024-00469-7","DOIUrl":"10.1038/s41434-024-00469-7","url":null,"abstract":"Gene therapy for CF has concentrated on targeting the lung. Here we took a different approach by injecting into the cephalic vein and spraying into the trachea of G551D, CF ferrets either AAV1 or 6 containing Δ27-264-CFTR, a truncated version of CFTR. Treatment with the potentiator VX-770 was halted for 7 days before instillation to induce a disease phenotype. Indeed, all ferrets were pancreas-insufficient when they entered the study. Four ferrets (three receiving AAV1 and one AAV6) were necropsied 48 days after vector delivery, and four (three receiving AAV6, one AAV1) were euthanized or died prior to the planned necropsy. AAV1 or AAV6 vector genomes, mRNA expression, and CFTR protein were detected in all tracheal and lung samples and in the liver, pancreas, and ileum of the treated ferrets. Surface and basal airway cells, pancreatic and bile ducts, and ileal crypts and villi were successfully transduced. Obstruction of the airways accompanied by pulmonary hemorrhaging, plugged pancreatic and bile ducts as well as mucous plugs in the ileum were noticed in untreated but absent from transduced ferrets necropsied at 48 days. Transduction of G551D ferrets suggests that a combination of systemic and airway application may be the preferred route of delivery for CF.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 9-10","pages":"499-510"},"PeriodicalIF":4.6,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00469-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777539","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

Gene drives: an alternative approach to malaria control? 基因驱动：疟疾控制的另一种方法？

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-07-22 DOI: 10.1038/s41434-024-00468-8

Kubendran Naidoo, Shüné V. Oliver

{"title":"Gene drives: an alternative approach to malaria control?","authors":"Kubendran Naidoo, Shüné V. Oliver","doi":"10.1038/s41434-024-00468-8","DOIUrl":"10.1038/s41434-024-00468-8","url":null,"abstract":"Genetic modification for the control of mosquitoes is frequently touted as a solution for a variety of vector-borne diseases. There has been some success using non-insecticidal methods like sterile or incompatible insect techniques to control arbovirus diseases. However, control by genetic modifications to reduce mosquito populations or create mosquitoes that are refractory to infection with pathogens are less developed. The advent of CRISPR-Cas9-mediated gene drives may advance this mechanism of control. In this review, use and progress of gene drives for vector control, particularly for malaria, is discussed. A brief history of population suppression and replacement gene drives in mosquitoes, rapid advancement of the field over the last decade and how genetic modification fits into the current scope of vector control are described. Mechanisms of alternative vector control by genetic modification to modulate mosquitoes’ immune responses and anti-parasite effector molecules as part of a combinational strategy to combat malaria are considered. Finally, the limitations and ethics of using gene drives for mosquito control are discussed.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"32 1","pages":"25-37"},"PeriodicalIF":4.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747935","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