• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

一种用于在原代人类细胞中递送CRISPR-Cas9并进行基因编辑的温度敏感且干扰素沉默的仙台病毒载体。

A temperature-sensitive and interferon-silent Sendai virus vector for CRISPR-Cas9 delivery and gene editing in primary human cells.

作者信息

Stevens Christian S, Carmichael Jillian, Watkinson Ruth, Kowdle Shreyas, Reis Rebecca A, Hamane Kory, Jang Jason, Park Arnold, Pernet Olivier, Khamaikawin Wannisa, Hong Patrick, Thibault Patricia, Gowlikar Aditya, An Dong Sung, Lee Benhur

机构信息

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.

UCLA School of Nursing, Los Angeles, California, 90095.

出版信息

bioRxiv. 2024 May 5:2024.05.03.592383. doi: 10.1101/2024.05.03.592383.

DOI:10.1101/2024.05.03.592383
PMID:38746439
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11092779/
Abstract

The transformative potential of gene editing technologies hinges on the development of safe and effective delivery methods. In this study, we developed a temperature-sensitive and interferon-silent Sendai virus (ts SeV) as a novel delivery vector for CRISPR-Cas9 and for efficient gene editing in sensitive human cell types without inducing IFN responses. ts SeV demonstrates unprecedented transduction efficiency in human CD34+ hematopoietic stem and progenitor cells (HSPCs) including transduction of the CD34+/CD38-/CD45RA-/CD90+(Thy1+)/CD49f stem cell enriched subpopulation. The frequency of editing exceeded 90% and bi-allelic editing exceeded 70% resulting in significant inhibition of HIV-1 infection in primary human CD14+ monocytes. These results demonstrate the potential of the ts SeV platform as a safe, efficient, and flexible addition to the current gene-editing tool delivery methods, which may help to further expand the possibilities in personalized medicine and the treatment of genetic disorders.

摘要

基因编辑技术的变革潜力取决于安全有效的递送方法的发展。在本研究中，我们开发了一种温度敏感且干扰素沉默的仙台病毒（ts SeV），作为一种新型递送载体用于CRISPR-Cas9，并在敏感的人类细胞类型中实现高效基因编辑而不诱导干扰素反应。ts SeV在人类CD34+造血干细胞和祖细胞（HSPCs）中展现出前所未有的转导效率，包括对CD34+/CD38-/CD45RA-/CD90+(Thy1+)/CD49f干细胞富集亚群的转导。编辑频率超过90%，双等位基因编辑超过70%，从而在原代人类CD14+单核细胞中显著抑制HIV-1感染。这些结果证明了ts SeV平台作为一种安全、高效且灵活的补充方法加入当前基因编辑工具递送方法的潜力，这可能有助于进一步拓展个性化医学和遗传疾病治疗的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/7974c0d9b642/nihpp-2024.05.03.592383v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/84d6ee4781dc/nihpp-2024.05.03.592383v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/222b132e5507/nihpp-2024.05.03.592383v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/38286cd28af7/nihpp-2024.05.03.592383v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/f8a5e034b819/nihpp-2024.05.03.592383v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/8ab42ae86ad7/nihpp-2024.05.03.592383v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/7974c0d9b642/nihpp-2024.05.03.592383v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/84d6ee4781dc/nihpp-2024.05.03.592383v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/222b132e5507/nihpp-2024.05.03.592383v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/38286cd28af7/nihpp-2024.05.03.592383v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/f8a5e034b819/nihpp-2024.05.03.592383v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/8ab42ae86ad7/nihpp-2024.05.03.592383v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc8/11092779/7974c0d9b642/nihpp-2024.05.03.592383v1-f0006.jpg

相似文献

1
A temperature-sensitive and interferon-silent Sendai virus vector for CRISPR-Cas9 delivery and gene editing in primary human cells.一种用于在原代人类细胞中递送CRISPR-Cas9并进行基因编辑的温度敏感且干扰素沉默的仙台病毒载体。
bioRxiv. 2024 May 5:2024.05.03.592383. doi: 10.1101/2024.05.03.592383.
2
Sendai virus, an RNA virus with no risk of genomic integration, delivers CRISPR/Cas9 for efficient gene editing.仙台病毒，一种没有基因组整合风险的 RNA 病毒，可递送 CRISPR/Cas9 进行高效的基因编辑。
Mol Ther Methods Clin Dev. 2016 Aug 24;3:16057. doi: 10.1038/mtm.2016.57. eCollection 2016.
3
Targeted, safe, and efficient gene delivery to human hematopoietic stem and progenitor cells in vivo using the engineered AVID adenovirus vector platform.利用工程化的 AVID 腺病毒载体平台，实现对人体内造血干细胞和祖细胞的靶向、安全、高效的基因传递。
Mol Ther. 2024 Jan 3;32(1):103-123. doi: 10.1016/j.ymthe.2023.10.023. Epub 2023 Nov 2.
4
CRISPR/Cas9-Mediated CCR5 Ablation in Human Hematopoietic Stem/Progenitor Cells Confers HIV-1 Resistance In Vivo.CRISPR/Cas9介导的人类造血干细胞/祖细胞中CCR5基因敲除在体内赋予对HIV-1的抗性
Mol Ther. 2017 Aug 2;25(8):1782-1789. doi: 10.1016/j.ymthe.2017.04.027. Epub 2017 May 17.
5
The CCR5 Gene Edited CD34CD90 Hematopoietic Stem Cell Population Serves as an Optimal Graft Source for HIV Gene Therapy.CCR5 基因编辑的 CD34CD90 造血干细胞群体可作为 HIV 基因治疗的最佳移植物来源。
Front Immunol. 2022 Mar 14;13:792684. doi: 10.3389/fimmu.2022.792684. eCollection 2022.
6
Combined lentiviral- and RNA-mediated CRISPR/Cas9 delivery for efficient and traceable gene editing in human hematopoietic stem and progenitor cells.联合慢病毒和 RNA 介导的 CRISPR/Cas9 递送系统用于高效且可追踪的人造血干/祖细胞基因编辑。
Sci Rep. 2020 Dec 28;10(1):22393. doi: 10.1038/s41598-020-79724-x.
7
CCR5 editing by Staphylococcus aureus Cas9 in human primary CD4 T cells and hematopoietic stem/progenitor cells promotes HIV-1 resistance and CD4 T cell enrichment in humanized mice.金黄色葡萄球菌 Cas9 对人源原代 CD4 T 细胞和造血干/祖细胞中的 CCR5 进行编辑可促进人源化小鼠中的 HIV-1 抗性和 CD4 T 细胞富集。
Retrovirology. 2019 Jun 11;16(1):15. doi: 10.1186/s12977-019-0477-y.
8
Genome editing in human hematopoietic stem and progenitor cells via CRISPR-Cas9-mediated homology-independent targeted integration.通过 CRISPR-Cas9 介导的非同源性靶向整合在人造血干/祖细胞中进行基因组编辑。
Mol Ther. 2021 Apr 7;29(4):1611-1624. doi: 10.1016/j.ymthe.2020.12.010. Epub 2020 Dec 10.
9
-Δ32 biology, gene editing, and warnings for the future of CRISPR-Cas9 as a human and humane gene editing tool.Δ32生物学、基因编辑以及对CRISPR-Cas9作为一种人类和人道基因编辑工具的未来警示。
Cell Biosci. 2020 Mar 30;10:48. doi: 10.1186/s13578-020-00410-6. eCollection 2020.
10
Optimization of CRISPR/Cas9 Delivery to Human Hematopoietic Stem and Progenitor Cells for Therapeutic Genomic Rearrangements.优化 CRISPR/Cas9 递送至人类造血干/祖细胞用于治疗性基因组重排。
Mol Ther. 2019 Jan 2;27(1):137-150. doi: 10.1016/j.ymthe.2018.10.008. Epub 2018 Oct 17.

本文引用的文献

1
Advances in the gene therapy of monogenic blood cell diseases.单基因血液疾病的基因治疗进展。
Clin Genet. 2020 Jan;97(1):89-102. doi: 10.1111/cge.13593. Epub 2019 Jul 11.
2
Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy.AAV-CRISPR 基因组编辑治疗杜氏肌营养不良症的长期评估。
Nat Med. 2019 Mar;25(3):427-432. doi: 10.1038/s41591-019-0344-3. Epub 2019 Feb 18.
3
CRISPR-Cas Biology and Its Application to Infectious Diseases.CRISPR-Cas 生物学及其在传染病中的应用。
J Clin Microbiol. 2019 Mar 28;57(4). doi: 10.1128/JCM.01307-18. Print 2019 Apr.
4
Removal of HIV DNA by CRISPR from Patient Blood Engrafts in Humanized Mice.利用CRISPR从人源化小鼠的患者血液移植物中去除HIV DNA。
Mol Ther Nucleic Acids. 2018 Sep 7;12:275-282. doi: 10.1016/j.omtn.2018.05.021. Epub 2018 Jun 19.
5
Meganuclease targeting of PCSK9 in macaque liver leads to stable reduction in serum cholesterol.靶向 PC SK9 的 Meganuclease 在猕猴肝脏中可稳定降低血清胆固醇。
Nat Biotechnol. 2018 Sep;36(8):717-725. doi: 10.1038/nbt.4182. Epub 2018 Jul 9.
6
Gene Editing on Center Stage.基因编辑站上舞台中央。
Trends Genet. 2018 Aug;34(8):600-611. doi: 10.1016/j.tig.2018.05.004. Epub 2018 Jun 13.
7
Delivering CRISPR: a review of the challenges and approaches.递送 CRISPR：挑战与方法综述
Drug Deliv. 2018 Nov;25(1):1234-1257. doi: 10.1080/10717544.2018.1474964.
8
Direct Promoter Repression by BCL11A Controls the Fetal to Adult Hemoglobin Switch.BCL11A 通过直接启动子抑制作用控制胎儿血红蛋白向成人血红蛋白的转变。
Cell. 2018 Apr 5;173(2):430-442.e17. doi: 10.1016/j.cell.2018.03.016. Epub 2018 Mar 29.
9
SaCas9 Requires 5'-NNGRRT-3' PAM for Sufficient Cleavage and Possesses Higher Cleavage Activity than SpCas9 or FnCpf1 in Human Cells.SaCas9 需要 5'-NNGRRT-3' 的原间隔序列邻近基序（PAM）来实现充分切割，并且在人类细胞中比 SpCas9 或 FnCpf1 具有更高的切割活性。
Biotechnol J. 2018 Mar;13(3):e1800080. doi: 10.1002/biot.201800080.
10
Efficient and Robust Reverse Genetics Systems.高效且稳健的反向遗传学系统
mSphere. 2017 Mar 29;2(2). doi: 10.1128/mSphere.00376-16. eCollection 2017 Mar-Apr.