Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis
Liver fibrosis is a wound-healing response that results from various chronic damages. If the causes of damage are not removed or effective treatments are not given in a timely manner, it will progress to cirrhosis, even liver cancer. Currently, there are no specific medical therapies for liver fibro...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050122000882 |
| _version_ | 1818535892124434432 |
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| author | Fang-tian Bu Peng-cheng Jia Yan Zhu Ya-ru Yang Hong-wu Meng Yi-hui Bi Cheng Huang Jun Li |
| author_facet | Fang-tian Bu Peng-cheng Jia Yan Zhu Ya-ru Yang Hong-wu Meng Yi-hui Bi Cheng Huang Jun Li |
| author_sort | Fang-tian Bu |
| collection | DOAJ |
| description | Liver fibrosis is a wound-healing response that results from various chronic damages. If the causes of damage are not removed or effective treatments are not given in a timely manner, it will progress to cirrhosis, even liver cancer. Currently, there are no specific medical therapies for liver fibrosis. Adeno-associated virus (AAV)-mediated gene therapy, one of the frontiers of modern medicine, has gained more attention in many fields due to its high safety profile, low immunogenicity, long-term efficacy in mediating gene expression, and increasingly known tropism. Notably, increasing evidence suggests a promising therapeutic potential for AAV-mediated gene therapy in different liver fibrosis models, which helps to correct abnormally changed target genes in the process of fibrosis and improve liver fibrosis at the molecular level. Moreover, the addition of cell-specific promoters to the genome of recombinant AAV helps to limit gene expression in specific cells, thereby producing better therapeutic efficacy in liver fibrosis. However, animal models are considered to be powerless predictive of tissue tropism, immunogenicity, and genotoxic risks in humans. Thus, AAV-mediated gene therapy will face many challenges. This review systemically summarizes the recent advances of AAV-mediated gene therapy in liver fibrosis, especially focusing on cellular and molecular mechanisms of transferred genes, and presents prospective challenges. |
| first_indexed | 2024-12-11T18:30:58Z |
| format | Article |
| id | doaj.art-ab0d40bbd2ac431cbecded088514156f |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-11T18:30:58Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-ab0d40bbd2ac431cbecded088514156f2022-12-22T00:54:56ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012022-09-0126191206Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosisFang-tian Bu0Peng-cheng Jia1Yan Zhu2Ya-ru Yang3Hong-wu Meng4Yi-hui Bi5Cheng Huang6Jun Li7Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 81 Mei Shan Road, Hefei, Anhui Province 230032, China; Institute for Liver Diseases of Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 81 Mei Shan Road, Hefei, Anhui Province 230032, China; Institute for Liver Diseases of Anhui Medical University, Hefei, ChinaThe First Affiliated Hospital of Anhui Medical University, Hefei, ChinaThe Second Affiliated Hospital of Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 81 Mei Shan Road, Hefei, Anhui Province 230032, China; Institute for Liver Diseases of Anhui Medical University, Hefei, ChinaThe Second Affiliated Hospital of Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 81 Mei Shan Road, Hefei, Anhui Province 230032, China; Institute for Liver Diseases of Anhui Medical University, Hefei, China; Corresponding author Cheng Huang, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 81 Mei Shan Road, Hefei, Anhui Province 230032, China.Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 81 Mei Shan Road, Hefei, Anhui Province 230032, China; Institute for Liver Diseases of Anhui Medical University, Hefei, China; Corresponding author Jun Li, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 81 Mei Shan Road, Hefei, Anhui Province 230032, China.Liver fibrosis is a wound-healing response that results from various chronic damages. If the causes of damage are not removed or effective treatments are not given in a timely manner, it will progress to cirrhosis, even liver cancer. Currently, there are no specific medical therapies for liver fibrosis. Adeno-associated virus (AAV)-mediated gene therapy, one of the frontiers of modern medicine, has gained more attention in many fields due to its high safety profile, low immunogenicity, long-term efficacy in mediating gene expression, and increasingly known tropism. Notably, increasing evidence suggests a promising therapeutic potential for AAV-mediated gene therapy in different liver fibrosis models, which helps to correct abnormally changed target genes in the process of fibrosis and improve liver fibrosis at the molecular level. Moreover, the addition of cell-specific promoters to the genome of recombinant AAV helps to limit gene expression in specific cells, thereby producing better therapeutic efficacy in liver fibrosis. However, animal models are considered to be powerless predictive of tissue tropism, immunogenicity, and genotoxic risks in humans. Thus, AAV-mediated gene therapy will face many challenges. This review systemically summarizes the recent advances of AAV-mediated gene therapy in liver fibrosis, especially focusing on cellular and molecular mechanisms of transferred genes, and presents prospective challenges.http://www.sciencedirect.com/science/article/pii/S2329050122000882liver fibrosisAAVgene therapyHSCscellular mechanism |
| spellingShingle | Fang-tian Bu Peng-cheng Jia Yan Zhu Ya-ru Yang Hong-wu Meng Yi-hui Bi Cheng Huang Jun Li Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis Molecular Therapy: Methods & Clinical Development liver fibrosis AAV gene therapy HSCs cellular mechanism |
| title | Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis |
| title_full | Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis |
| title_fullStr | Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis |
| title_full_unstemmed | Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis |
| title_short | Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis |
| title_sort | emerging therapeutic potential of adeno associated virus mediated gene therapy in liver fibrosis |
| topic | liver fibrosis AAV gene therapy HSCs cellular mechanism |
| url | http://www.sciencedirect.com/science/article/pii/S2329050122000882 |
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