Review
Genetics & Heredity
Xiangjun He, Brian Anugerah Urip, Zhenjie Zhang, Chun Christopher Ngan, Bo Feng
Summary: In recent years, gene therapy has entered a new era with AAV emerging as a potent vector for gene transfer in vivo. AAV-based gene therapy products have been approved by FDA and EMA for the treatment of previously incurable diseases, marking significant progress in the field. The combination of AAV vectors with genome editing tools has introduced new therapeutic modalities, expanding treatment options for untreatable diseases.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Review
Cell Biology
Shaza S. Issa, Alisa A. Shaimardanova, Valeriya V. Solovyeva, Albert A. Rizvanov
Summary: Despite the advancements in gene and cell therapy, some diseases still lack effective treatment. Adeno-associated viruses (AAVs) have enabled the development of effective gene therapy methods for various diseases. Numerous AAV-based gene therapy medications are undergoing trials and entering the market. This article provides a review of AAV discovery, properties, serotypes, tropism, and their applications in gene therapy for different diseases of organs and systems.
Article
Immunology
David Brown, Michael Altermatt, Tatyana Dobreva, Sisi Chen, Alexander Wang, Matt Thomson, Viviana Gradinaru
Summary: Engineered variants of recombinant adeno-associated viruses are rapidly being developed to meet the demand for gene therapy delivery vehicles with specific cell-type and tissue tropisms. An experimental and computational single-cell RNA sequencing pipeline has been developed to characterize barcoded rAAV pools at high resolution, revealing both confirmed and unidentified AAV capsid targeting biases.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Dongsheng Duan
Summary: This mini-review summarizes clinical findings of lethal immunotoxicity induced by high-dose systemic AAV gene therapy and calls for collaborative efforts to better understand the underlying mechanisms and develop effective prevention/treatment strategies.
Review
Pharmacology & Pharmacy
Paul Young
Summary: Advanced therapy medicinal products have extended the treatment paradigm to gene therapy, which modifies genes for therapeutic effect. Gene therapy has strong growth potential, especially using adeno-associated viruses (AAVs) for targeted delivery. However, manufacturing challenges exist in generating high-quality and efficacious viral vectors. Learning from established processes like monoclonal antibody production and embracing innovative approaches are crucial for scalable and cost-effective solutions. Ultimately, the goal is to turn treatment into a cure.
DRUG DISCOVERY TODAY
(2023)
Review
Pharmacology & Pharmacy
Paul Young
Summary: Advanced therapy medicinal products have expanded the treatment options in the pharmaceutical industry by enabling gene therapy for potentially curative approaches, primarily using adeno-associated viruses (AAVs) for targeted delivery. However, manufacturing challenges exist in ensuring high quality and efficacy of AAV-based gene therapy products. Learning from established manufacturing processes like monoclonal antibodies (mAbs) can help develop scalable and cost-effective solutions. Future innovation and collaboration with regulatory agencies are essential for further advancements in gene therapy manufacturing and achieving the ultimate goal of cure.
DRUG DISCOVERY TODAY
(2023)
Article
Immunology
Bradley A. Hamilton, J. Fraser Wright
Summary: This article discusses the host immune responses that limit durable therapeutic gene expression in AAV-based human gene therapies. A strategy of removing pathogen-associated molecular patterns in AAV vector genomes to overcome immunological barriers is proposed.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Thomas Weber
Summary: AAV vector-based gene therapy is currently the only approved in vivo gene therapy in the US and Europe, but the presence of pre-existing anti-AAV antibodies presents a formidable challenge to its successful clinical use. Establishing protocols to determine relevant titers of these antibodies and methods to deplete them is now more urgent than ever to ensure the efficacy of AAV gene transfer therapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Jiaming Wang, Yue Zhang, Craig A. Mendonca, Onur Yukselen, Khaja Muneeruddin, Lingzhi Ren, Jialing Liang, Chen Zhou, Jun Xie, Jia Li, Zhong Jiang, Alper Kucukural, Scott A. Shaffer, Guangping Gao, Dan Wang
Summary: Gene therapy is a potential cure for currently untreatable diseases. This study demonstrates the successful use of recombinant adeno-associated virus (rAAV) to deliver suppressor tRNA (rAAV.sup-tRNA) and effectively treat a genetic disease in a mouse model with a nonsense mutation. The treatment lasted for more than 6 months and showed promising results for various target tissues. This research highlights the feasibility and potential benefits of using rAAV-delivered nonsense suppressor tRNAs to rescue pathogenic nonsense mutations.
Review
Cardiac & Cardiovascular Systems
Huili Zhang, Qi Zhan, Biao Huang, Yigang Wang, Xiaoyan Wang
Summary: Gene therapy has brought significant advancements to the field of medicine, offering hope for patients with various diseases. Adeno-associated virus (AAV) has shown great potential as a treatment tool due to its safety, sustainable gene expression, and low immunogenicity, especially in the field of cardiovascular disease.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Maxim A. Korneyenkov, Andrey A. Jr Jr Zamyatnin
Summary: AAV is a popular choice for gene therapy delivery, but its unspecific tissue tropism is a serious limitation. Recent techniques have been developed to produce highly selective and targeted AAV capsids, although it is still far from the ideal state. Despite drawbacks and limitations, other approaches are still in play in the field of AAV research.
Review
Immunology
Xuefeng Li, Xiaoli Wei, Jinduan Lin, Li Ou
Summary: Recombinant adeno-associated virus (AAV) has shown great potential as a delivery vehicle for gene therapy, but immune response issues need to be addressed for its effective clinical application.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Hematology
Weijie Li
Summary: In this study, Calabria et al demonstrate that intrathymic delivery of AAV vectors leads to site-specific integration within TCR genes close to DNA breaks created by RAG enzymes during V(D)J recombination.
Article
Biotechnology & Applied Microbiology
Drew H. Bryant, Ali Bashir, Sam Sinai, Nina K. Jain, Pierce J. Ogden, Patrick F. Riley, George M. Church, Lucy J. Colwell, Eric D. Kelsic
Summary: The study uses deep learning to design highly diverse AAV2 capsid protein variants viable for packaging DNA payload, surpassing the average diversity of natural AAV serotype sequences. Deep neural network models accurately predict capsid viability across diverse variants even when trained on limited data, unlocking previously unreachable sequence space with many potential applications.
NATURE BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Agata Antepowicz, Omar Habib, Freja Kirsebom, Cecilia Johansson, Deborah R. Gill, Stephen C. Hyde
Summary: In this study, gene delivery approaches using recombinant adeno-associated virus and simian immunodeficiency virus vectors were utilized to achieve sustained in vivo production of Palivizumab in a murine model. Pre-treatment with Palivizumab-expressing vectors provided complete protection against RSV-induced weight loss. This approach offers prophylaxis against RSV infection, potentially reducing treatment costs in vulnerable populations.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Jing Gao, Dongsheng Wang, Dan Liu, Min Liu, Yehua Ge, Minghong Jiang, Yanxin Liu
MOLECULAR BIOLOGY OF THE CELL
(2015)
Article
Oncology
Zhenbiao Xu, Lianmei Zhao, Xin Yang, Sisi Ma, Yehua Ge, Yanxin Liu, Shilian Liu, Juan Shi, Dexian Zheng
Article
Biochemistry & Molecular Biology
Lianmei Zhao, Taotao Han, Yanshuang Li, Jiazeng Sun, Shang Zhang, Yanxin Liu, Baoen Shan, Dexian Zheng, Juan Shi
Article
Biochemistry & Molecular Biology
Longfei Chen, Yuhe Qiu, Zhenliang Hao, Jiong Cai, Shuyong Zhang, Yanxin Liu, Dexian Zheng
Article
Medicine, Research & Experimental
Sisi Ma, Jiazeng Sun, Yabin Guo, Peng Zhang, Yanxin Liu, Dexian Zheng, Juan Shi
Article
Physiology
Jiazeng Sun, Shang Zhang, Bianhua Shi, Dexian Zheng, Juan Shi
FRONTIERS IN PHYSIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Hui Guo, Lianmei Zhao, Bianhua Shi, Jiayu Bao, Dexian Zheng, Baoguo Zhou, Juan Shi
Article
Oncology
Liu Zheng, Zhang Weilun, Jiang Minghong, Zhang Yaxi, Liu Shilian, Liu Yanxin, Zheng Dexian
Article
Oncology
Zhijuan Diao, Juan Shi, Jieqing Zhu, Haiqin Yuan, Qiang Ru, Shilian Liu, Yanxin Liu, Dexian Zheng
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2013)
Article
Biochemistry & Molecular Biology
Dongsheng Wang, Dan Liu, Jing Gao, Min Liu, Shilian Liu, Minghong Jiang, Yanxin Liu, Dexian Zheng
Article
Immunology
Jieqing Zhu, Longfei Chen, Juan Shi, Shilian Liu, Yanxin Liu, Dexian Zheng
Article
Biochemistry & Molecular Biology
Yuhe Qiu, Zhixin Zhang, Juan Shi, Shilian Liu, Yanxin Liu, Dexian Zheng
Article
Biotechnology & Applied Microbiology
Meng Li, Yaomin Wu, Yuhe Qiu, Zhenyu Yao, Shilian Liu, Yanxin Liu, Juan Shi, Dexian Zheng
Article
Medicine, Research & Experimental
Shuyong Zhang, Chao Zheng, Wan Zhu, Peng Xiong, Dongdong Zhou, Changjiang Huang, Dexian Zheng
Article
Rheumatology
Ting Zhang, Huihua Li, Juan Shi, Sha Li, Muyuan Li, Lei Zhang, Leting Zheng, Dexian Zheng, Fulin Tang, Xuan Zhang, Fengchun Zhang, Xin You
ARTHRITIS RESEARCH & THERAPY
(2016)
Article
Medicine, Research & Experimental
Yuwen Zhu, Yan Guo, Yujia Xue, Anqi Zhou, Ying Chen, Yifei Chen, Xiulian Miao, Fangqiao Lv
Summary: BRG1 plays an important role in HSC-myofibroblast transition and targeting it could be a reasonable strategy for liver fibrosis intervention.
Article
Medicine, Research & Experimental
Liu Ye, Beibei Liu, Jingling Huang, Xiaolin Zhao, Yuan Wang, Yungen Xu, Shuping Wang
Summary: Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Article
Medicine, Research & Experimental
Jiahui Yang, Xiaoyu Chen, Tianjing Liu, Yongyan Shi
Summary: This article reviews the role of bile acids in necrotizing enterocolitis (NEC) and their potential therapeutic value. The dysregulation of bile acids is associated with intestinal injury, and inflammatory factors in the liver also play a crucial role in regulating bile acid transport. The bile acid metabolic pathway is important for regulating intestinal microbiota, cell proliferation, and barrier protection.
Review
Medicine, Research & Experimental
Zhenzheng Zhu, Yuemiao Xu, Yuwei Xia, Xinru Jia, Yixin Chen, Yuyue Liu, Leyin Zhang, Hui Chai, Leitao Sun
Summary: Bile acid, as the final product of cholesterol breakdown, plays a complex regulatory and signaling role in human metabolism. Research suggests that it has the potential to enhance metabolism and regulate chronic metabolic diseases through various pathways. The interaction between bile acid and gut microbiota is also of great significance.
Article
Medicine, Research & Experimental
Xin He, Hong-Xu Zhou, Xian Fu, Kai-Di Ni, Ai-Zhi Lin, Ling-Tong Zhang, Hou-Hua Yin, Qing Jiang, Xue Zhou, Yi-Wen Meng, Jun-Yan Liu
Summary: DON exposure causes an increase in deoxycholic acid (DCA), which contributes to intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.
Article
Medicine, Research & Experimental
Zhitao Wang, Heng Ma, Abdul Nasir, Sufang Liu, Zhisong Li, Feng Tao, Qian Bai
Summary: This study reveals the involvement of TET1-mediated epigenetic regulation in chronic TMJ pain through trigeminal TNF alpha signaling.
Article
Medicine, Research & Experimental
Lu Yu, Hao Ran, Yaru Lu, Qian Ma, Huan Huang, Weibin Liu
Summary: This study found that the HIF-1 alpha inhibitor BAY 87-2243 can alleviate the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model. BAY 87-2243 can restore the balance of CD4(+)T cell subsets, reduce the production of pro-inflammatory cytokines, and act as both an immune imbalance regulator and anti-inflammatory.
Article
Medicine, Research & Experimental
Alex Peralvarez-Marin, Montse Sole, Judith Serrano, Alice Taddeucci, Belen Perez, Clara Penas, Gemma Manich, Marcel Jimenez, Pilar D'Ocon, Francesc Jimenez-Altayo
Summary: This study provides the first evidence that TRPV2 channels may modulate vascular tone by balancing opposing inputs from the endothelium and smooth muscle, leading to net vasodilation. The amplification of TRPV2 channel-induced activity by NO emphasizes the pathophysiological relevance of these findings.
Article
Medicine, Research & Experimental
Amin Ullah, Jing Zhao, Jiakun Li, Rajeev K. Singla, Bairong Shen
Summary: Gastric cancer is the fifth-most prevalent and second-most deadly cancer worldwide. Late onset of symptoms makes early detection important. CXC chemokines play an important role in the pathological process of gastric cancer, but their exact role in diagnosis and prognosis is not fully understood. Inhibiting CXC chemokines shows promise as a targeted therapy.
Article
Medicine, Research & Experimental
Menna S. Zeyada, Salma M. Eraky, Mamdouh M. El-Shishtawy
Summary: The current study demonstrates the prophylactic and antifibrotic effects of Trig against BLM-induced PF by targeting multiple signaling pathways. The combination of Trig and Pirf may be a promising approach to enhance Pirf's anti-fibrotic effect.