Pub Date : 2024-08-26DOI: 10.1038/s41434-024-00481-x
Henna Korpela, Jaakko Lampela, Jonna Airaksinen, Niko Järveläinen, Satu Siimes, Kaisa Valli, Tiina Nieminen, Minttu Turunen, Maria Grönman, Antti Saraste, Juhani Knuuti, Mikko Hakulinen, Pekka Poutiainen, Vesa Kärjä, Jussi Nurro, Seppo Ylä-Herttuala
{"title":"Correction: AAV2-VEGF-B gene therapy failed to induce angiogenesis in ischemic porcine myocardium due to inflammatory responses","authors":"Henna Korpela, Jaakko Lampela, Jonna Airaksinen, Niko Järveläinen, Satu Siimes, Kaisa Valli, Tiina Nieminen, Minttu Turunen, Maria Grönman, Antti Saraste, Juhani Knuuti, Mikko Hakulinen, Pekka Poutiainen, Vesa Kärjä, Jussi Nurro, Seppo Ylä-Herttuala","doi":"10.1038/s41434-024-00481-x","DOIUrl":"10.1038/s41434-024-00481-x","url":null,"abstract":"","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 11-12","pages":"626-628"},"PeriodicalIF":4.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00481-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072560","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}
Pub Date : 2024-08-25DOI: 10.1038/s41434-024-00480-y
Alexandra McCarron, Kak-Ming Ling, Samuel T. Montgomery, Kelly M. Martinovich, Patricia Cmielewski, Nathan Rout-Pitt, Anthony Kicic, David Parsons, Martin Donnelley
Mutation-agnostic treatments such as airway gene therapy have the potential to treat any individual with cystic fibrosis (CF), irrespective of their CF transmembrane conductance regulator (CFTR) gene variants. The aim of this study was to employ two CF rat models, Phe508del and CFTR knockout (KO), to assess the comparative effectiveness of CFTR modulators and lentiviral (LV) vector-mediated gene therapy. Cells were isolated from the tracheas of rats and used to establish air-liquid interface (ALI) cultures. Phe508del rat ALIs were treated with the modulator combination, elexacaftor-tezacaftor-ivacaftor (ETI), and separate groups of Phe508del and KO tracheal epithelial cells were treated with LV-CFTR followed by differentiation at ALI. Ussing chamber measurements were performed to assess CFTR function. ETI-treated Phe508del ALI cultures demonstrated CFTR function that was 59% of wild-type level, while gene-addition therapy restored Phe508del to 68% and KO to 47% of wild-type level, respectively. Our findings show that rat Phe508del-CFTR protein can be successfully rescued with ETI treatment, and that CFTR gene-addition therapy provides significant CFTR correction in Phe508del and KO ALI cultures to levels that were comparable to ETI. These findings highlight the potential of an LV vector-based gene therapy for the treatment of CF lung disease.
气道基因疗法等突变识别疗法有可能治疗任何囊性纤维化（CF）患者，无论其CF跨膜传导调节器（CFTR）基因变异情况如何。本研究的目的是利用两种CF大鼠模型（Phe508del和CFTR基因敲除（KO））来评估CFTR调节剂和慢病毒（LV）载体介导的基因疗法的比较效果。从大鼠气管中分离出细胞，用于建立气液界面（ALI）培养物。用调节剂组合 elexacaftor-tezacaftor-ivacaftor (ETI) 处理 Phe508del 大鼠 ALI，用 LV-CFTR 处理不同组的 Phe508del 和 KO 气管上皮细胞，然后在 ALI 上进行分化。进行乌星室测量以评估 CFTR 功能。经 ETI 处理的 Phe508del ALI 培养物的 CFTR 功能仅为野生型的 59%，而经基因添加疗法处理的 Phe508del 和 KO 细胞的 CFTR 功能分别恢复到野生型的 68% 和 47%。我们的研究结果表明，大鼠 Phe508del-CFTR 蛋白可通过 ETI 治疗成功挽救，而 CFTR 基因添加疗法可显著纠正 Phe508del 和 KO ALI 培养物中的 CFTR，使其达到与 ETI 相当的水平。这些发现凸显了基于 LV 载体的基因疗法治疗 CF 肺病的潜力。
{"title":"Lentiviral vector gene therapy and CFTR modulators show comparable effectiveness in cystic fibrosis rat airway models","authors":"Alexandra McCarron, Kak-Ming Ling, Samuel T. Montgomery, Kelly M. Martinovich, Patricia Cmielewski, Nathan Rout-Pitt, Anthony Kicic, David Parsons, Martin Donnelley","doi":"10.1038/s41434-024-00480-y","DOIUrl":"10.1038/s41434-024-00480-y","url":null,"abstract":"Mutation-agnostic treatments such as airway gene therapy have the potential to treat any individual with cystic fibrosis (CF), irrespective of their CF transmembrane conductance regulator (CFTR) gene variants. The aim of this study was to employ two CF rat models, Phe508del and CFTR knockout (KO), to assess the comparative effectiveness of CFTR modulators and lentiviral (LV) vector-mediated gene therapy. Cells were isolated from the tracheas of rats and used to establish air-liquid interface (ALI) cultures. Phe508del rat ALIs were treated with the modulator combination, elexacaftor-tezacaftor-ivacaftor (ETI), and separate groups of Phe508del and KO tracheal epithelial cells were treated with LV-CFTR followed by differentiation at ALI. Ussing chamber measurements were performed to assess CFTR function. ETI-treated Phe508del ALI cultures demonstrated CFTR function that was 59% of wild-type level, while gene-addition therapy restored Phe508del to 68% and KO to 47% of wild-type level, respectively. Our findings show that rat Phe508del-CFTR protein can be successfully rescued with ETI treatment, and that CFTR gene-addition therapy provides significant CFTR correction in Phe508del and KO ALI cultures to levels that were comparable to ETI. These findings highlight the potential of an LV vector-based gene therapy for the treatment of CF lung disease.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 11-12","pages":"553-559"},"PeriodicalIF":4.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00480-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055383","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}
Pub Date : 2024-08-16DOI: 10.1038/s41434-024-00478-6
F. Sarinella, A. Calistri, P. Sette, G. Palù, C. Parolin
{"title":"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","authors":"F. Sarinella, A. Calistri, P. Sette, G. Palù, C. Parolin","doi":"10.1038/s41434-024-00478-6","DOIUrl":"10.1038/s41434-024-00478-6","url":null,"abstract":"","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 9-10","pages":"530-530"},"PeriodicalIF":4.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00478-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995645","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}
Pub Date : 2024-08-15DOI: 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
{"title":"Correction: Alternative oxidase encoded by sequence-optimized and chemically-modified RNA transfected into mammalian cells is catalytically active","authors":"Luca Giordano, Manish K. Aneja, Natascha Sommer, Nasim Alebrahimdehkordi, Alireza Seraji, Norbert Weissmann, Carsten Rudolph, Christian Plank, Howard T. Jacobs, Marten Szibor","doi":"10.1038/s41434-024-00473-x","DOIUrl":"10.1038/s41434-024-00473-x","url":null,"abstract":"","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 9-10","pages":"528-528"},"PeriodicalIF":4.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00473-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987783","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}
Pub Date : 2024-08-15DOI: 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
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.
{"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}
Pub Date : 2024-08-12DOI: 10.1038/s41434-024-00477-7
Mengtian Cui, Qin Su, Mitchell Yip, Jackson McGowan, Claudio Punzo, Guangping Gao, Phillip W. L. Tai
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.
{"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}
Pub Date : 2024-08-07DOI: 10.1038/s41434-024-00474-w
Rafael J. Yáñez-Muñoz, Jane E. Itzhaki
{"title":"Correction: Andrew C. G. Porter (1955–2023)","authors":"Rafael J. Yáñez-Muñoz, Jane E. Itzhaki","doi":"10.1038/s41434-024-00474-w","DOIUrl":"10.1038/s41434-024-00474-w","url":null,"abstract":"","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 9-10","pages":"529-529"},"PeriodicalIF":4.6,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00474-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901451","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}
Pub Date : 2024-08-01DOI: 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
{"title":"Correction: Limited potential of AAV-mediated gene therapy in transducing human mesenchymal stem cells for bone repair applications","authors":"Sofia Bougioukli, Morgan Chateau, Heidy Morales, Venus Vakhshori, Osamu Sugiyama, Daniel Oakes, Donald Longjohn, Paula Cannon, Jay R. Lieberman","doi":"10.1038/s41434-024-00472-y","DOIUrl":"10.1038/s41434-024-00472-y","url":null,"abstract":"","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 9-10","pages":"527-527"},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00472-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874629","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}
Pub Date : 2024-07-29DOI: 10.1038/s41434-024-00470-0
Rafael J. Yáñez-Muñoz, Jane E. Itzhaki
{"title":"Andrew C. G. Porter (1955–2023)","authors":"Rafael J. Yáñez-Muñoz, Jane E. Itzhaki","doi":"10.1038/s41434-024-00470-0","DOIUrl":"10.1038/s41434-024-00470-0","url":null,"abstract":"","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"31 9-10","pages":"437-438"},"PeriodicalIF":4.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-024-00470-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792303","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}
Pub Date : 2024-07-28DOI: 10.1038/s41434-024-00471-z
Mansi Tiwari, Ahlima Roumane, Nadine Sommer, Weiping Han, Mirela Delibegović, Justin J. Rochford, George D. Mcilroy
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.
{"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}
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