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CRISPR-Cas9 for medical genetic screens: applications and future perspectives
  1. Hui-Ying Xue1,
  2. Li-Juan Ji2,
  3. Ai-Mei Gao3,
  4. Ping Liu4,
  5. Jing-Dong He5,
  6. Xiao-Jie Lu6
  1. 1The Reproductive Center, Jiangsu Huai'an Maternity and Children Hospital, Huai'an, China
  2. 2Department of Rehabilitation, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, China
  3. 3Department of Pharmacy, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
  4. 4Department of Pathology, Shiyan Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, China
  5. 5Department of Clinical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China
  6. 6Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
  1. Correspondence to Dr He Jing-Dong, Department of Clinical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China; 13861596338@126.com Dr Xiao-Jie Lu, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, No150, Jimo Rode, Shanghai 200092, China; 189@whu.edu.cn

Abstract

CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) systems have emerged as versatile and convenient (epi)genome editing tools and have become an important player in medical genetic research. CRISPR-Cas9 and its variants such as catalytically inactivated Cas9 (dead Cas9, dCas9) and scaffold-incorporating single guide sgRNA (scRNA) have been applied in various genomic screen studies. CRISPR screens enable high-throughput interrogation of gene functions in health and diseases. Compared with conventional RNAi screens, CRISPR screens incur less off-target effects and are more versatile in that they can be used in multiple formats such as knockout, knockdown and activation screens, and can target coding and non-coding regions throughout the genome. This powerful screen platform holds the potential of revolutionising functional genomic studies in the near future. Herein, we introduce the mechanisms of (epi)genome editing mediated by CRISPR-Cas9 and its variants, introduce the procedures and applications of CRISPR screen in functional genomics, compare it with conventional screen tools and at last discuss current challenges and opportunities and propose future directions.

  • Genetics
  • Genetic screening/counselling
  • Genome-wide

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