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T细胞的基因改造

Genetic Modification of T Cells.

作者信息

Morgan Richard A, Boyerinas Benjamin

机构信息

Bluebird bio, 150 Second Street, Cambridge, MA 02141, USA.

出版信息

Biomedicines. 2016 Apr 20;4(2):9. doi: 10.3390/biomedicines4020009.

DOI:10.3390/biomedicines4020009
PMID:28536376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5344249/
Abstract

Gene transfer technology and its application to human gene therapy greatly expanded in the last decade. One area of investigation that appears particularly promising is the transfer of new genetic material into T cells for the potential treatment of cancer. Herein, we describe several core technologies that now yield high-efficiency gene transfer into primary human T cells. These gene transfer techniques include viral-based gene transfer methods based on modified and non-viral methods such as DNA-based transposons and direct transfer of mRNA by electroporation. Where specific examples are cited, we emphasize the transfer of chimeric antigen receptors (CARs) to T cells, which permits engineered T cells to recognize potential tumor antigens.

摘要

在过去十年中,基因转移技术及其在人类基因治疗中的应用得到了极大的扩展。一个特别有前景的研究领域是将新的遗传物质导入T细胞以用于癌症的潜在治疗。在此,我们描述了几种目前能高效地将基因导入原代人T细胞的核心技术。这些基因转移技术包括基于病毒的基因转移方法(基于修饰的病毒)以及非病毒方法,如基于DNA的转座子和通过电穿孔直接转移mRNA。在引用具体例子时,我们强调了嵌合抗原受体(CAR)向T细胞的转移,这使得工程化T细胞能够识别潜在的肿瘤抗原。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2599/5344249/32735e89474b/biomedicines-04-00009-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2599/5344249/f516a271fb1e/biomedicines-04-00009-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2599/5344249/ff3c31550778/biomedicines-04-00009-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2599/5344249/cfb13b249ec6/biomedicines-04-00009-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2599/5344249/32735e89474b/biomedicines-04-00009-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2599/5344249/f516a271fb1e/biomedicines-04-00009-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2599/5344249/ff3c31550778/biomedicines-04-00009-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2599/5344249/cfb13b249ec6/biomedicines-04-00009-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2599/5344249/32735e89474b/biomedicines-04-00009-g004.jpg

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本文引用的文献

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Manufacture of T cells using the Sleeping Beauty system to enforce expression of a CD19-specific chimeric antigen receptor.使用 Sleeping Beauty 系统制造 T 细胞以强制表达 CD19 特异性嵌合抗原受体。
Cancer Gene Ther. 2015 Mar;22(2):95-100. doi: 10.1038/cgt.2014.69. Epub 2015 Jan 16.
3
Alpharetroviral vectors: from a cancer-causing agent to a useful tool for human gene therapy.
病毒和非病毒系统将基因治疗递送至临床靶标。
Int J Mol Sci. 2024 Jul 4;25(13):7333. doi: 10.3390/ijms25137333.
4
Engineering strategies to safely drive CAR T-cells into the future.工程化策略助力 CAR T 细胞安全迈入未来。
Front Immunol. 2024 Jun 19;15:1411393. doi: 10.3389/fimmu.2024.1411393. eCollection 2024.
5
Advanced strategies in improving the immunotherapeutic effect of CAR-T cell therapy.提高CAR-T细胞疗法免疫治疗效果的先进策略。
Mol Oncol. 2024 Aug;18(8):1821-1848. doi: 10.1002/1878-0261.13621. Epub 2024 Mar 8.
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AAV-mediated delivery of a Sleeping Beauty transposon and an mRNA-encoded transposase for the engineering of therapeutic immune cells.腺相关病毒介导的沉睡美人转座子和 mRNA 编码的转座酶的递送,用于治疗性免疫细胞的工程改造。
Nat Biomed Eng. 2024 Feb;8(2):132-148. doi: 10.1038/s41551-023-01058-6. Epub 2023 Jul 10.
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Mol Ther Nucleic Acids. 2014 Jul 29;3(7):e179. doi: 10.1038/mtna.2014.33.
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