欧美成一级-欧美成在人线a免费-欧美传媒影-欧美大逼逼-欧美大成色www永久网站婷-欧美大胆a级视频

新聞動態(tài)
企業(yè)新聞
媒體報道
發(fā)表文獻

Published PAPER發(fā)表文獻

  • 2024

    Xue N., Hong D., Zhang D., et al. Engineering IscB to develop highly efficient miniature editing tools in mammalian cells and embryos. Molecular Cell (2024).

  • 2024

    Wang X., Wu X., Tan B., et al. Allogeneic CD19-targeted CAR-T therapy in severe myositis and systemic sclerosis achieved durable remission and reversed extensive fibrotic damages. Cell (2024).

  • 2024

    Yang L., Huo Y., Wang M., et al. Engineering APOBEC3A deaminase for highly accurate and efficient base editing. Nature Chemical Biology (2024).

  • 2023

    Zhang, N., Liu, X., Qin, J., et al. LIGHT/TNFSF14 promotes CAR-T cell trafficking and cytotoxicity through reversing immunosuppressive tumor microenvironment. Molecular Therapy (2023).

  • 2023

    Chen, L., Hong, M., Luan, C., et al. Adenine transversion editors enable precise, efficient A·T-to-C?G base editing in mammalian cells and embryos. Nature Biotechnology (2023).

  • 2022

    Chen, L., Zhu, B., Ru, G., et al. Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing. Nature Biotechnology (2022).

  • 2022

    Chen, L., Zhang, S., Xue, N., et al. Engineering a precise adenine base editor with minimal bystander editing. Nature Chemical Biology (2022).

  • 2022

    Zhang, J., Hu, Y., Yang, J., et al. Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL. Nature (2022).

    Recently, chimeric antigen receptor (CAR)-T cell therapy has shown great promise in treating haematological malignancies1–7 . However, CAR-T cell therapy currently has several limitations8–12. Here we successfully developed a two-in-one approach to generate non-viral, gene-specifc targeted CAR-T cells through CRISPR–Cas9. Using the optimized protocol, we demonstrated feasibility in a preclinical study by inserting an anti-CD19 CAR cassette into the AAVS1 safe-harbour locus. Furthermore, an innovative type of anti-CD19 CAR-T cell with PD1 integration was developed and showed superior ability to eradicate tumour cells in xenograft models. In adoptive therapy for relapsed/refractory aggressive B cell non-Hodgkin lymphoma (ClinicalTrials.gov, NCT04213469), we observed a high rate (87.5%) of complete remission and durable responses without serious adverse events in eight patients. Notably, these enhanced CAR-T cells were efective even at a low infusion dose and with a low percentage of CAR+ cells. Single-cell analysis showed that the electroporation method resulted in a high percentage of memory T cells in infusion products, and PD1 interference enhanced anti-tumour immune functions, further validating the advantages of non-viral, PD1-integrated CAR-T cells. Collectively, our results demonstrate the high safety and efcacy of non-viral, gene-specifc integrated CAR-T cells, thus providing an innovative technology for CAR-T cell therapy.
  • 2022

    Fu, B., Liao, J., Chen, S. et al. CRISPR–Cas9-mediated gene editing of the BCL11A enhancer for pediatric β0/β0 transfusion-dependent β-thalassemia. Nature Medicine (2022).

    Gene editing to disrupt the GATA1-binding site at the +58 BCL11A erythroid enhancer could induce γ-globin expression, which is a promising therapeutic strategy to alleviate β-hemoglobinopathy caused by HBB gene mutation. In the present study, we report the preliminary results of an ongoing phase 1/2 trial (NCT04211480) evaluating safety and efficacy of gene editing therapy in children with blood transfusion-dependent β-thalassemia (TDT). We transplanted BCL11A enhancer-edited, autologous, hematopoietic stem and progenitor cells into two children, one carrying the β0/β0 genotype, classified as the most severe type of TDT. Primary endpoints included engraftment, overall survival and incidence of adverse events (AEs). Both patients were clinically well with multilineage engraftment, and all AEs to date were considered unrelated to gene editing and resolved after treatment. Secondary endpoints included achieving transfusion independence, editing rate in bone marrow cells and change in hemoglobin (Hb) concentration. Both patients achieved transfusion independence for >18?months after treatment, and their Hb increased from 8.2 and 10.8?g?dl?1 at screening to 15.0 and 14.0?g?dl?1 at the last visit, respectively, with 85.46% and 89.48% editing persistence in bone marrow cells. Exploratory analysis of single-cell transcriptome and indel patterns in edited peripheral blood mononuclear cells showed no notable side effects of the therapy.
  • 2020

    Zhang, X., Zhu, B., Chen, L.?et al.?Dual base editor catalyzes both cytosine and adenine base conversions in human cells.?Nature Biotechnology (2020).

    Although base editors are useful tools for precise genome editing, current base editors can only convert either adenines or cytosines. We developed a dual adenine and cytosine base editor (A&C-BEmax) by fusing both deaminases with a Cas9 nickase to achieve C-to-T and A-to-G conversions at the same target site. Compared to single base editors, A&C-BEmax’s activity on adenines is slightly reduced, whereas activity on cytosines is higher and RNA off-target activity is substan- tially decreased.
  • 2020

    Zhang X., Chen L., Zhu B., et al. Increasing the efficiency and targeting range of cytidine base editors through fusion of a single-stranded DNA-binding protein domain. Nature Cell Biology (2020).

    Cytidine base editors are powerful genetic tools that catalyse cytidine to thymidine conversion at specific genomic loci, and further improvement of the editing range and efficiency is critical for their broader applications. Through insertion of a non-sequence-specific single-stranded DNA-binding domain from Rad51 protein between Cas9 nickase and the deaminases, serial hyper cytidine base editors were generated with substantially increased activity and an expanded editing window towards the protospacer adjacent motif in both cell lines and mouse embryos. Additionally, hyeA3A-BE4max selectively cata- lysed cytidine conversion in TC motifs with a broader editing range and much higher activity (up to 257-fold) compared with eA3A-BE4max. Moreover, hyeA3A-BE4max specifically generated a C-to-T conversion without inducing bystander mutations in the haemoglobin gamma gene promoter to mimic a naturally occurring genetic variant for amelioration of β-haemoglobinopathy, suggesting the therapeutic potential of the improved base editors.
  • 2020

    Zeng J, Wu Y, Ren C, Bauer DE, et al. Therapeutic base editing of human hematopoietic stem cells. Nature Medicine, 2020.

    Base editing by nucleotide deaminases linked to programmable DNA-binding proteins represents a promising approach to permanently remedy blood disorders, although its application in engrafting hematopoietic stem cells (HSCs) remains unexplored. Here we purified A3A (N57Q)-BE3 protein for ribonucleoprotein (RNP) electroporation of human peripheral blood (PB) mobilized CD34+ hematopoietic stem and progenitor cells (HSPCs). We observed frequent on-target cytosine base
請輸入您想查 |
返回頂部
主站蜘蛛池模板: 日产中文字乱码卡一卡二卡 | 欧美最新免费一 | 欧美日产国产精品 | 亚洲一级片在线观看 | 国产大码无尺度视频在线 | 国产欧美在线综合一区 | 亚洲影视网| 欧美一区二区三区在线 | 2025国产| 日本深夜福利在线观看不卡高清 | 成人无码电影在线 | 欧美vide| www.中文字幕在线 | 欧美激情视频一区 | 日本不卡免费新一区二区三区 | 国产欧美日韩综合精品一级 | 国产99久久九九精品无码 | 国产素人视频在线播放 | 欧美日韩中文精品在线 | 黑人巨大两根一起挤进a片视 | 欧美亚洲另类 | 在线成人免费观看国产精品 | 精品久久久久免费极品大片 | 91免费人成网站在线观看18 | 日韩国产欧美中文字幕 | 国产亚洲精久久久久久无码 | 成在人线av无码免观看麻豆 | 亚洲国产成人aⅴ毛片大全 亚洲国产成人av网站 | 国产免费中文字幕v在线 | 蜜桃91丨九色丨蝌蚪 | 娇妻4p被八个男人伺候电影 | 国产乱子伦视频大全 | 亚洲日韩小电影在线观看 | 午夜福利国产极品福利 | 国产精品三级无码不卡在线 | 日本丰满b| 国产精品一区二区高清久久久 | 97精品一区二区视频在线观看 | 国产精品成人99久久久久麻豆 | 97久久精品人人操人妻人 | 99精品国产在热久久婷婷 |