Article
Biochemistry & Molecular Biology
Yeon-Suk Yang, Chujiao Lin, Hong Ma, Jun Xie, Frederick S. Kaplan, Guangping Gao, Jae-Hyuck Shim
Summary: Gene therapy using adeno-associated virus has been developed to suppress trauma-induced heterotopic ossification in mice with fibrodysplasia ossificans progressiva (FOP), while limiting expression in non-skeletal organs. The therapy effectively inhibits aberrant signaling pathway activation and osteogenic differentiation in skeletal progenitor cells.
Article
Medicine, Research & Experimental
Dongxin Wang, Qungang Zhou, Xiang Qiu, Xiaomei Liu, Chun Zhang
Summary: This study optimized the protocol for rAAV6 transduction of primary T cells, significantly improved the expression efficiency of the rAAV6 delivered CAR gene, and successfully generated rAAV6-based CAR-T cells (AAV-CAR-T). The findings provide an efficient method for AAV transduction of T cells and an alternative way for the preparation of CAR-T cells.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Immunology
Gongqiang Wu, Shanshan Guo, Qian Luo, Xiaoxia Wang, Wenhai Deng, Guifang Ouyang, Jeffrey J. Pu, Wen Lei, Wenbin Qian
Summary: This study identified anti-CD70 CAR-T cells as a potential new treatment for AML. However, this CAR-T cell therapy did not completely eliminate leukemia in vivo, suggesting the need for further research and development of innovative combinatorial CAR constructs and increased CD70 expression on leukemia cell surface to optimize CAR-T cell responses for AML.
FRONTIERS IN IMMUNOLOGY
(2023)
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
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)
Article
Multidisciplinary Sciences
Elisa Ruffo, Adam A. Butchy, Yaniv Tivon, Victor So, Michael Kvorjak, Avani Parikh, Eric L. Adams, Natasa Miskov-Zivanov, Olivera J. Finn, Alexander Deiters, Jason Lohmueller
Summary: This study introduces engineered cell-surface receptors called chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors, which can sense target antigens and respond accordingly. The authors develop universal receptor systems that can be post-translationally directed to specific antigens through covalent attachment of BG-conjugated antibodies. They demonstrate successful targeting of SNAP-CAR and SNAP-synNotch receptors using clinically relevant BG-conjugated antibodies, showing anti-tumor activity in a human tumor xenograft mouse model. A mathematical model is also developed to better understand the parameters affecting universal receptor signaling.
NATURE COMMUNICATIONS
(2023)
Review
Endocrinology & Metabolism
Laura Skukan, Matea Brezak, Rok Ister, Lars Klimaschewski, Aleksandar Vojta, Vlatka Zoldos, Srecko Gajovic
Summary: Most of the 87 selected publications focused on using adult male rodents, with the preferred stroke model being transient middle cerebral artery occlusion. Both LV and AAV vectors were equally utilized for transgene delivery, although AAVs had higher loads than LVs. The meta-analysis based on infarct volume as the primary outcome demonstrated the effectiveness of preclinical interventions, despite the presence of publication bias and setbacks in terms of bias risks and study relevance. Increasing translational potential may involve specific cell targeting, post-stroke interventions, non-invasive systematic delivery, and the utilization of large animals.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Biotechnology & Applied Microbiology
Evangelia Kokalaki, Biao Ma, Mathieu Ferrari, Thomas Grothier, Warren Hazelton, Somayya Manzoor, Eren Costu, Julia Taylor, Anna Bulek, Saket Srivastava, Isaac Gannon, Ram Jha, Rosalind Gealy, Lukas Stanczuk, Tatiana Rizou, Mathew Robson, Mohamed El-Kholy, Vania Baldan, Matteo Righi, James Sillibourne, Simon Thomas, Shimobi Onuoha, Shaun Cordoba, Martin Pule
Summary: CART cells recognizing CD19 effectively treat relapsed and refractory B-ALL and DLBCL, but CD19 loss often leads to relapse. Targeting a second antigen, CD22, can reduce antigen escape, but it is challenging due to low CD22 density and large structure. The characteristics and optimal strategy for CD22 CAR are not well-studied. Co-administration of CD19 and CD22 CARs is costly, and constructing single CARs targeting both antigens is difficult. A dual CART product, CAT/9A8 CART, is being tested in a phase I clinical study as a potential solution.
Article
Cell Biology
Mayumi Sugita, Takahiro Yamazaki, Mohammad Alhomoud, Jeremie Martinet, Jean-Baptiste Latouche, Encouse Golden, Olivier Boyer, Koen Van Besien, Silvia C. Formenti, Lorenzo Galluzzi, Monica L. Guzman
Summary: Autologous T cells engineered with CAR specific for CD19 have been approved for treating CD19(+) hematological malignancies. However, relapse often occurs when neoplastic cells lose CD19 expression. Preclinical models have shown that radiation therapy (RT) can overcome CD19 loss by inducing death receptor expression in cancer cells. Using a human model of CD19(+) acute lymphoblastic leukemia (ALL), it was found that low-dose total body irradiation (LD-TBI) administered before CAR T cell infusion significantly improved overall survival and CAR T cell expansion. These findings support the initiation of clinical trials combining LD-TBI with CAR T cells.
CELL DEATH & DISEASE
(2023)
Review
Immunology
Hildegund C. J. Ertl
Summary: Adeno-associated virus (AAV)-mediated gene transfer has shown benefits in treating patients with inherited diseases like hemophilia B, but challenges remain due to potential rejection of AAV-transduced cells. Immunosuppression may prevent rejection in some patients. CD8(+) T cells induced by AAV infections may recognize AAV vector's capsids and eliminate cells expressing degraded capsid antigens, or AAV vectors themselves may induce de novo T cell responses, particularly at high doses. This chapter discusses strategies to prevent activation of CD8(+) T cell responses to AAV infections and gene transfer.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Engineering, Biomedical
Neha N. Parayath, Matthias T. Stephan
Summary: Gene therapy enables the creation of CAR-T cells to target specific diseases, but current manufacturing protocols are costly and complex, limiting access for many patients. In vivo programming of T cells could potentially overcome these challenges and expand the reach of this therapy.
ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 23, 2021
(2021)
Article
Medicine, Research & Experimental
Haixia Li, Dani Zhong, Huiguan Luo, Wei Shi, Shenxia Xie, Hangbiao Qiang, Lichen Zhu, Li Gao, Jun Liu, Shuyang Sun, Ziqiang Ding, Xiaomei Yang, Xiaoling Lu
Summary: Chimeric antigen receptor (CAR) T-cell immunotherapy is a research hotspot in the field of malignant tumor treatment. This study investigates whether nanobody-based T cell receptor-like CAR T cells can target intracellular antigens and effectively kill tumor cells. By developing HLA-A2/GPC3 and HLA-A2/WT1-specific nanobodies and incorporating them into TCR-like CARs, the researchers found that these CAR-redirected T cells could selectively recognize and kill MHC/peptide complex-expressing tumor cells both in vitro and in mouse tumor models. This study offers a potential strategy to target intracellular antigens and expand the application of CAR T-cell therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Medicine, Research & Experimental
Nicholas Buss, Lisa Lanigan, Jillynne Zeller, Derek Cissell, Monica Metea, Eric Adams, Mikayla Higgins, Kwi Hye Kim, Ewa Budzynski, Lin Yang, Ye Liu, Mark Butt, Olivier Danos, Michele Fiscella
Summary: Recent studies have shown that non-human primates administered with recombinant adeno-associated viruses (rAAVs) develop lesions in the dorsal root ganglia (DRG). In this study, different purification methods were used to produce rAAV9s, and the results indicate that regardless of purification methods, DRG lesions were observed in monkeys. The lesions included neuronal degeneration, increased cellularity, and nerve fiber degeneration. Furthermore, MRI revealed an increase in short tau inversion recovery (STIR) intensity and a decrease in fractional anisotropy in animals with axonopathy. However, animals administered with the Null AAV9 vector did not develop DRG lesions, despite the presence of vector DNA at similar or higher levels compared to rAAV9-treated animals.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Biotechnology & Applied Microbiology
Samanta Romina Zanetti, Talia Velasco-Hernandez, Francisco Gutierrez-Aguera, Victor M. Diaz, Paola Alejandra Romecin, Heleia Roca-Ho, Diego Sanchez-Martinez, Nestor Tirado, Matteo Libero Baroni, Paolo Petazzi, Raul Torres-Ruiz, Oscar Molina, Alex Bataller, Jose Luis Fuster, Paola Ballerini, Manel Juan, Irmela Jeremias, Clara Bueno, Pablo Menendez
Summary: CD19-directed CAR T cells have achieved impressive response rates in B-ALL, but relapse remains a challenge. A tandem CAR targeting both CD19 and CD22 showed similar efficacy as CD19-CAR in vitro and in vivo. It is worth exploring whether this approach can enhance leukemia eradication and reduce relapse rates.
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
Multidisciplinary Sciences
Peixin Song, Nan Zheng, Yong Liu, Chen Tian, Xilin Wu, Xiaohua Ma, Deyan Chen, Xue Zou, Guiyang Wang, Huanru Wang, Yongyang Zhang, Sufang Lu, Chao Wu, Zhiwei Wu
NATURE COMMUNICATIONS
(2018)
Review
Engineering, Biomedical
Waqas Nawaz, Shijie Xu, Yanlei Li, Bilian Huang, Xilin Wu, Zhiwei Wu
ACTA BIOMATERIALIA
(2020)
Article
Medicine, Research & Experimental
Xilin Wu, Yanlei Li, Bilian Huang, Xiaohua Ma, Linjing Zhu, Nan Zheng, Shijie Xu, Waqas Nawaz, Changping Xu, Zhiwei Wu
Article
Biotechnology & Applied Microbiology
Xue Zou, Meng Yuan, Tongyu Zhang, Nan Zheng, Zhiwei Wu
Summary: This study engineered mammalian extracellular vesicles (EVs) to deliver interferon-induced transmembrane protein 3 (IFITM3) for the treatment of Zika virus (ZIKV) infection. The results demonstrated that IFITM3-containing EVs (IFITM3-Exos) significantly reduced ZIKV viremia in pregnant mice and effectively delivered IFITM3 protein across the placental barrier to suppress the virus in fetuses. Mechanistic study revealed that IFITM3 inhibited viral entry by targeting late endosomes/lysosomes.
Article
Microbiology
Shijie Xu, Na Jiang, Waqas Nawaz, Bingxin Liu, Fang Zhang, Ye Liu, Xilin Wu, Zhiwei Wu
Summary: SFTSV, a tick-borne emerging phlebovirus, has high mortality rates and lacks specific therapies. Previous models have limitations in understanding the pathogenesis of SFTSV infection, urging the development of suitable small animal models for research.
Article
Immunology
Rui Zhang, Min Cheng, Bingxin Liu, Meng Yuan, Deyan Chen, Yujiong Wang, Zhiwei Wu
Summary: DDX6, a DEAD-box RNA helicase, plays a crucial role in anti-Enterovirus 71 activity by enhancing RIG-I-mediated interferon response. However, EV71 has evolved a strategy to antagonize the antiviral effect of DDX6 by proteolytic degradation of the molecule using its non-structural protein 2A.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Rui Zhang, Yuxuan Fu, Min Cheng, Wenyuan Ma, Nan Zheng, Yongxiang Wang, Zhiwei Wu
Summary: The research team has developed a targeted antiviral therapy system based on sEVs to combat ZIKV-induced neurological disorders and fetal brain infections. This system utilizes specific siRNA and neuron-targeting proteins, effectively preventing infection in fetal mouse brains and alleviating neuroinflammation and neurological damage caused by ZIKV.
Article
Cell Biology
Xilin Wu, Lin Cheng, Ming Fu, Bilian Huang, Linjing Zhu, Shijie Xu, Haixia Shi, Doudou Zhang, Huanyun Yuan, Waqas Nawaz, Ping Yang, Qinxue Hu, Yalan Liu, Zhiwei Wu
Summary: Neutralizing nanobodies derived from an alpaca immunized with SARS-CoV-2 spike glycoprotein show potential therapeutic effects against COVID-19. A trimer of Nbs, Nb-15-NbH-Nb-15, exhibits high neutralization potency against SARS-CoV-2 live virus and variants with a long half-life. Intranasal administration of Nb-15-Nb-H-Nb-15 provides effective protection against SARS-CoV-2 infection in transgenic hACE2 mice for both prophylactic and therapeutic purposes.
Article
Microbiology
Deyan Chen, Ye Liu, Fang Zhang, Qiao You, Wenyuan Ma, Jing Wu, Zhiwei Wu
Summary: The study found that 6-TG inhibits multiple strains of HSV1 infection, including ACV-resistant strains, more effectively than ACV and GCV. 6-TG applied topically to eyes with HSV-1 infection significantly inhibits virus replication, alleviates HSK pathogenesis, and improves eye conditions. Knockdown of Rac1 with siRNA restricts HSV-1 replication, indicating Rac1's role in the pathogenesis of HSK.
MICROBIOLOGY SPECTRUM
(2021)
Article
Immunology
Xilin Wu, Yaxing Wang, Lin Cheng, Fengfeng Ni, Linjing Zhu, Sen Ma, Bilian Huang, Mengmeng Ji, Huimin Hu, Yuncheng Li, Shijie Xu, Haixia Shi, Doudou Zhang, Linshuo Liu, Waqas Nawaz, Qinxue Hu, Sheng Ye, Yalan Liu, Zhiwei Wu
Summary: Current COVID-19 vaccines take at least one month to become effective and around 51% of the global population is still not fully vaccinated. This study introduces a nanobody called Nb22 which has ultrapotent neutralization against the Delta variant and can remain in the respiratory system for a long period of time. Intranasal administration of Nb22 provides instantaneous short-term prophylaxis against SARS-CoV-2.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Jing Wu, Qiao You, Ruining Lyu, Yajie Qian, Hongji Tao, Fang Zhang, Yurong Cai, Na Jiang, Nan Zheng, Deyan Chen, Zhiwei Wu
Summary: This study evaluated the regulatory role of folate metabolism in the antiviral innate immune response. The results showed that folate metabolism negatively regulated OAS-mediated antiviral innate immune response and was involved in the ADAR3/endogenous dsRNA/OAS axis. Injection of an A-to-I editing inhibitor in experimental animals enhanced the antiviral innate immune response. These findings provide a new perspective for the treatment of RNA viral infectious diseases by targeting the ADAR3/endogenous dsRNA/OAS axis.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)