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Size and Structure of Viral Genomes01:26

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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非ウイルスゲノム標的化によるヒトT細胞機能と特異性の再プログラム

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.

Nature
|July 12, 2018
PubMed
まとめ

この研究では,非ウイルス性CRISPR-Cas9ゲノム編集システムを導入し,T細胞を再プログラムします. この方法は,自己免疫疾患の矯正や癌の免疫療法を含む治療用途のための正確な大規模なDNA挿入を可能にします.

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科学分野:

  • 免疫学
  • 分子生物学
  • 遺伝子療法

背景:

  • 伝統的なT細胞再プログラミングは ウイルスベクトルに依存し 費用がかかり 時間がかかります
  • ウイルスのベクトルには 精密なゲノム統合が欠けていて 治療応用には 課題があります
  • ゲノム編集は標的型の遺伝子挿入を提供しているが,大きなDNA配列では限界に直面している.

研究 の 目的:

  • 主要なヒトT細胞に高効率でサイト固有の大型DNA配列を挿入するための非ウイルスCRISPR-Cas9システムを開発する.
  • 遺伝的欠陥の修正と癌の免疫療法のためのT細胞の設計における このシステムの治療的可能性を実証する.

主な方法:

  • CRISPR-Cas9ゲノムターゲティングシステムを開発し,大型DNA配列 (> 1kb) の非ウイルス性,ホモロジー指向の修復媒介挿入を行いました.
  • 主要なヒトT細胞にシステムを適用し,細胞の生存能力,機能,精密なゲノム統合を評価した.
  • このシステムを活用して,自己免疫疾患モデルにおける IL2RA 変異を修正し,がんを標的とする T 細胞受容体 (TCR) を搭載した T 細胞を設計した.

主要な成果:

  • ウイルスのベクトルなしで,主要なヒトT細胞に,大規模なDNA配列を迅速かつ効率的に挿入し,細胞の生存能力と機能を保ちました.
  • 病原性IL2RA変異を成功裏に修正し,単発性自己免疫疾患患者のT細胞のシグナル伝達機能を回復しました.
  • 腫瘍抗原を特定する新しいTCRを持つT細胞は,in vitroとin vivoで有効な抗腫瘍反応を示しています.

結論:

  • 非ウイルス性CRISPR-Cas9ゲノムターゲティングシステムは,ヒトの原始免疫細胞の迅速かつ柔軟な遺伝子工学を可能にします.
  • この技術は,自己免疫疾患や癌に対する 新しい細胞ベースの治療法の開発に 重要な臨床前期的な可能性を秘めています
  • 非ウイルスゲノムターゲティングは,T細胞ベースの治療のためのウイルスベクトルのより効率的で潜在的に費用対効果の高い代替手段を提供します.