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Size and Structure of Viral Genomes

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Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
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Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
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Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
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In Vivo Direct Reprogramming of Resident Glial Cells into Interneurons by Intracerebral Injection of Viral Vectors
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通过非病毒基因组向重新编程人类T细胞功能和特异性

Theodore L Roth1,2,3,4,5, Cristina Puig-Saus6, Ruby Yu3,4,5

  • 1Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA.

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|July 12, 2018
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概括

这项研究引入了非病毒CRISPR-Cas9基因组编辑系统,以实现有效的T细胞重编程. 这种方法使得精确的大型DNA插入用于治疗,包括自身免疫性疾病的纠正和癌症免疫疗法.

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科学领域:

  • 免疫学
  • 分子生物学
  • 基因治疗

背景情况:

  • 传统的T细胞重新编程依赖于病毒载体,
  • 病毒载体缺乏精确的基因组整合,这给治疗应用带来了挑战.
  • 基因组编辑提供了有针对性的基因插入,但面临着大型DNA序列的限制.

研究的目的:

  • 开发一种非病毒的CRISPR-Cas9系统,以高效地将大型DNA序列插入到人类T细胞中.
  • 证明该系统在纠正基因缺陷和用于癌症免疫治疗的T细胞方面的治疗潜力.

主要方法:

  • 开发了CRISPR-Cas9基因组向系统,用于非病毒性,同质导向的修复介导的大型DNA序列的插入.
  • 将该系统应用于初级人类T细胞,评估细胞活力,功能和精确的基因组整合.
  • 利用该系统在自身免疫性疾病模型中纠正IL2RA突变,并将T细胞与向癌症的T细胞受体 (TCR) 进行工程.

主要成果:

  • 在没有病毒载体的情况下快速有效地将大型DNA序列插入到人类T细胞中,从而保持细胞活力和功能.
  • 成功纠正了致病性IL2RA突变,恢复了单一自身免疫性疾病患者T细胞的信号功能.
  • 具有新型TCR的工程T细胞专门识别瘤抗原,在体外和体内表现出有效的抗瘤反应.

结论:

  • 非病毒CRISPR-Cas9基因组向系统能够快速灵活地对人类原发性免疫细胞进行基因工程.
  • 这项技术对于开发用于自身免疫性疾病和癌症的基于细胞的新疗法具有显著的临床前前景.
  • 非病毒基因组向为基于T细胞的疗法提供了比病毒载体更有效,更具成本效益的替代方案.