2017 Vol. 8(8)

The life and work of Dr. Fan Qingsheng: a pioneer in antibiotics research, agricultural microbiology, systems agriculture, and agricultural education in China
Jianping Xu
2017, 8(8): 551-557. doi: 10.1007/s13238-017-0374-x
Editing base in mouse model
Haoyi Wang
2017, 8(8): 558-559. doi: 10.1007/s13238-017-0432-4
The minor collagens in articular cartilage
Yunyun Luo, Dovile Sinkeviciute, Yi He, Morten Karsdal, Yves Henrotin, Ali Mobasheri, Patrik Önnerfjord, Anne Bay-Jensen
2017, 8(8): 560-572. doi: 10.1007/s13238-017-0377-7
Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type Ⅱ collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type IV, VI, IX, X, XI, XⅡ, XⅢ, and XIV, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials.
Increasing the safety and efficacy of chimeric antigen receptor T cell therapy
Hua Li, Yangbing Zhao
2017, 8(8): 573-589. doi: 10.1007/s13238-017-0411-9
Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumorassociated immune suppression, and using gene editing technologies to generate universal CAR T cells. All these efforts promote the development and evolution of CAR T cell therapy and move toward our ultimate goal-curing cancer with high safety, high efficacy, and low cost.
Research articles
The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection
Xuyuan Zhang, Pan Yang, Nan Wang, Jialong Zhang, Jingyun Li, Hao Guo, Xiangyun Yin, Zihe Rao, Xiangxi Wang, Liguo Zhang
2017, 8(8): 590-600. doi: 10.1007/s13238-017-0405-7
Entero virus 71 (EV71) causes hand, foot, and mouth disease (HFMD) and occasionally leads to severe neurological complications and even death. Scavenger receptor class B member 2 (SCARB2) is a functional receptor for EV71, that mediates viral attachment, internalization, and uncoating. However, the exact binding site of EV71 on SCARB2 is unknown. In this study, we generated a monoclonal antibody (mAb) that binds to human but not mouse SCARB2. It is named JL2, and it can effectively inhibit EV71 infection of target cells. Using a set of chimeras of human and mouse SCARB2, we identified that the region containing residues 77-113 of human SCARB2 contributes significantly to JL2 binding. The structure of the SCARB2-JL2 complex revealed that JL2 binds to the apical region of SCARB2 involving α-helices 2, 5, and 14. Our results provide new insights into the potential binding sites for EV71 on SCARB2 and the molecular mechanism of EV71 entry.
Effective gene editing by high-fidelity base editor 2 in mouse zygotes
Puping Liang, Hongwei Sun, Ying Sun, Xiya Zhang, Xiaowei Xie, Jinran Zhang, Zhen Zhang, Yuxi Chen, Chenhui Ding, Yuanyan Xiong, Wenbin Ma, Dan Liu, Junjiu Huang, Zhou Songyang
2017, 8(8): 601-611. doi: 10.1007/s13238-017-0418-2
Targeted point mutagenesis through homologous recombination has been widely used in genetic studies and holds considerable promise for repairing diseasecausing mutations in patients. However, problems such as mosaicism and low mutagenesis efficiency continue to pose challenges to clinical application of such approaches. Recently, a base editor (BE) system built on cytidine (C) deaminase and CRISPR/Cas9 technology was developed as an alternative method for targeted point mutagenesis in plant, yeast, and human cells. Base editors convert C in the deamination window to thymidine (T) efficiently, however, it remains unclear whether targeted base editing in mouse embryos is feasible. In this report, we generated a modified highfidelity version of base editor 2 (HF2-BE2), and investigated its base editing efficacy in mouse embryos. We found that HF2-BE2 could convert C to T efficiently, with up to 100% biallelic mutation efficiency in mouse embryos. Unlike BE3, HF2-BE2 could convert C to T on both the target and non-target strand, expanding the editing scope of base editors. Surprisingly, we found HF2-BE2 could also deaminate C that was proximal to the gRNA-binding region. Taken together, our work demonstrates the feasibility of generating point mutations in mouse by base editing, and underscores the need to carefully optimize base editing systems in order to eliminate proximal-site deamination.
CLE42 binding induces PXL2 interaction with SERK2
Shulin Mou, Xiaoxiao Zhang, Zhifu Han, Jiawei Wang, Xinqi Gong, Jijie Chai
2017, 8(8): 612-617. doi: 10.1007/s13238-017-0435-1
Screening novel stress granule regulators from a natural compound library
Li-Dan Hu, Xiang-Jun Chen, Xiao-Yan Liao, Yong-Bin Yan
2017, 8(8): 618-622. doi: 10.1007/s13238-017-0430-6
Energy-coupling mechanism of the multidrug resistance transporter AcrB: Evidence for membrane potential-driving hypothesis through mutagenic analysis
Min Liu, Xuejun C. Zhang
2017, 8(8): 623-627. doi: 10.1007/s13238-017-0417-3

Current Issue

March, 2019

Volume 10, Issue 3

Pages 157-233

About the cover

Metastasis is the leading cause of human cancer deaths.Unfortunately, no approved drugs are available for antimetastatic treatment. In this study, high-throughputsequencing-based high-throughput screening (HTS2) anda breast cancer lung metastasis (BCLM)-associated genesignature were combined to discover anti-metastatic drugs.After screening of thousands of compounds, Shao et al.identifed Ponatinib as a BCLM inhibitor. Ponatinib signifcantlyinhibited the migration and mammosphere formation of breastcancer cells in vitro and blocked BCLM in multiple mousemodels. This study may facilitate the therapeutic treatment ofBCLM as well as other metastases.

Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang Beijing 100101, China

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