Biologics: Targets & Therapy (Jan 2024)

Recent Advancements in Reducing the Off-Target Effect of CRISPR-Cas9 Genome Editing

  • Asmamaw Mengstie M,
  • Teshome Azezew M,
  • Asmamaw Dejenie T,
  • Teshome AA,
  • Tadele Admasu F,
  • Behaile Teklemariam A,
  • Tilahun Mulu A,
  • Mekonnen Agidew M,
  • Adugna DG,
  • Geremew H,
  • Abebe EC

Journal volume & issue
Vol. Volume 18
pp. 21 – 28

Abstract

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Misganaw Asmamaw Mengstie,1 Muluken Teshome Azezew,2 Tadesse Asmamaw Dejenie,3 Assefa Agegnehu Teshome,4 Fitalew Tadele Admasu,1 Awgichew Behaile Teklemariam,1 Anemut Tilahun Mulu,1 Melaku Mekonnen Agidew,1 Dagnew Getnet Adugna,5 Habtamu Geremew,6 Endeshaw Chekol Abebe1 1Department of Biochemistry, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia; 2Department of Physiology, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia; 3Department of Medical Biochemistry, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 4Department of Anatomy, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia; 5Department of Anatomy, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 6College of Health Sciences, Oda Bultum University, Chiro, EthiopiaCorrespondence: Misganaw Asmamaw Mengstie, Department of Biochemistry, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia, Tel +25196715350, Email [email protected]: The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)) and the associated protein (Cas9) system, a young but well-studied genome-editing tool, holds plausible solutions to a wide range of genetic disorders. The single-guide RNA (sgRNA) with a 20-base user-defined spacer sequence and the Cas9 endonuclease form the core of the CRISPR-Cas9 system. This sgRNA can direct the Cas9 nuclease to any genomic region that includes a protospacer adjacent motif (PAM) just downstream and matches the spacer sequence. The current challenge in the clinical applications of CRISPR-Cas9 genome-editing technology is the potential off-target effects that can cause DNA cleavage at the incorrect sites. Off-target genome editing confuses and diminishes the therapeutic potential of CRISPR-Cas9 in addition to potentially casting doubt on scientific findings regarding the activities of genes. In this review, we summarize the recent technological advancements in reducing the off-target effect of CRISPR-Cas9 genome editing.Keywords: CRISPR-Cas9, genome editing, off-target effect, recent advancements, review

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