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相关概念视频

CRISPR/Cas9 Genome Editing01:28

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The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
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Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
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CRISPR01:59

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Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats is a adaptive immune system found in bacteria and archaea that protects against viral infections. This system enables prokaryotic cells to identify, remember, and neutralize foreign genetic elements, primarily bacteriophages, by storing fragments of the invader’s DNA as a genetic memory.The CRISPR immune response begins during an initial infection. Cas (CRISPR-associated) proteins play a central role in this...
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可编程的结合式CRISPR干扰向肠道中的基因毒素.

Brian Hamp1, Hania Timek1, Chengyuan Fang1,2

  • 1Department of Biomedical Engineering, College of Engineering and School of Medicine, University of Michigan, Ann Arbor, MI, 48109, United States.

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概括

由等离子体传递的工程CRISPR干扰 (CRISPRi) 沉默了大肠杆菌 (Escherichia coli) 的菌素生产,降低了小鼠的基因毒性和结直肠癌风险. 这种可编程的活体生物治疗方法提供了一种针对微生物代谢物的新策略.

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科学领域:

  • 微生物学 微生物学
  • 遗传学 遗传学 是一个
  • 在瘤学瘤学.

背景情况:

  • 科利巴克丁是一种由*pks*+*Escherichia coli*产生的基因毒素,越来越多地与早期结直肠癌有关.
  • 目前没有批准的治疗药物直接针对胆固醇菌素的生产.
  • 现有的细菌抑制方法可能会导致耐药性突变.

研究的目的:

  • 设计一种新的系统,以有针对性地抑制*pks*+*E. coli*中的*colibactin生物合成.
  • 在小鼠模型中评估该系统在减少细菌基因毒性,殖民和瘤发生方面的有效性.
  • 建立一个可编程活体生物治疗的多功能平台,针对微生物代谢物.

主要方法:

  • 开发一种自我传播的结合性等离子体,以提供CRISPR干扰 (CRISPRi) 系统.
  • 在 *pks*+ *E. coli* 菌株中,通过 CRISPRi 中介抑制了 colibactin 生物合成基因.
  • 在小鼠体内测试以评估减少DNA损伤,细菌殖民和瘤发生.

主要成果:

  • 设计的CRISPRi系统成功地使 colibactin 生产沉默,并消除了 *pks*+ *E. coli* 的基因毒性,而没有诱导耐药性突变.
  • 结合介导的CRISPRi减少了小鼠的DNA损伤和*pks*+*E. coli*殖民,同时保持了肠道共生多样性.
  • 在小鼠结直肠癌模型中,该系统在降低瘤发生方面表现出比药物抑制剂更高的疗效.

结论:

  • 结合介导的CRISPRi系统提供了一种强有力的策略,可以抑制胆固醇菌素的产生并减轻与之相关的健康风险.
  • 这种可编程的活体生物治疗平台可扩展,可以中和其他致病性微生物代谢物.
  • 开发的系统扩大了工程肠道细菌作为治疗剂的工具包.