豚内生レトロウイルス (PERV) の全ゲノム不活性化

Luhan Yang¹, Marc Güell², Dong Niu³

¹Department of Genetics, Harvard Medical School, Boston, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. eGenesis Biosciences, Boston, MA 02115, USA. gchurch@genetics.med.harvard.edu luhan.yang@egenesisbio.com.

Science (New York, N.Y.)

|October 13, 2015

まとめ

科学者はCRISPR-Cas9を使って豚の腎臓細胞から全ての豚内生レトロウイルス (PERV) を除去しましたこの突破はPERVの伝播を大幅に減らし安全な異種移植の道を開きます

科学分野:

遺伝学
ウイルス学
移植科学

背景:

臓器移植は臓器提供者の不足に直面しています
豚の臓器は潜在的な解決策ですが,豚内生レトロウイルス (PERVs) は異種移植の重要な安全性問題です.
PERVは豚から人間に伝染する可能性があるので,無効化が必要である.

研究の目的:

豚腎上皮質細胞系 (PK15) のすべての豚内生レトロウイルス (PERV) を根絶する.
複数のPERVコピーを破壊する CRISPR-Cas9の有効性を評価する
遺伝子組み換え後のPERVのヒト細胞への感染の減少を評価する.

主な方法:

PK15 細胞のPERV コピー番号 (62 コピー) を決定した.
すべての特定されたコピーのPERVポリゲンを破壊するためにCRISPR-Cas9遺伝子編集を使用した.
PERV伝播を定量化するために,ヒト細胞とPK15細胞を共培養した.

主要な成果:

PK15細胞系にある 62個のPERVポリン遺伝子を全て破壊しました.
遺伝子組み換え細胞を用いてPERVのヒト細胞への感染を1000倍以上減少させました.
CRISPR- Cas9の多重化性が高いことが示され,最大62の遺伝子コピーを標的とした.

結論:

CRISPR-Cas9は豚の細胞で PERVsを無効化する強力なツールです.
PK15細胞におけるPERVsの根絶は,種間感染のリスクを大幅に軽減します.
この研究は,PERVで不活性化された豚の臓器のヒト異種移植の潜在的な臨床応用を支持する.

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