Journal article
Off-Target Analysis in Gene Editing and Applications for Clinical Translation of CRISPR/Cas9 in HIV-1 Therapy
Frontiers in genome editing, v 3, pp 673022-673022
17 Aug 2021
PMID: 34713260
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
As genome-editing nucleases move toward broader clinical applications, the need to define the limits of their specificity and efficiency increases. A variety of approaches for nuclease cleavage detection have been developed, allowing a full-genome survey of the targeting landscape and the detection of a variety of repair outcomes for nuclease-induced double-strand breaks. Each approach has advantages and disadvantages relating to the means of target-site capture, target enrichment mechanism, cellular environment, false discovery, and validation of bona fide off-target cleavage sites in cells. This review examines the strengths, limitations, and origins of the different classes of off-target cleavage detection systems including anchored primer enrichment (GUIDE-seq),
in situ
detection (BLISS),
in vitro
selection libraries (CIRCLE-seq), chromatin immunoprecipitation (ChIP) (DISCOVER-Seq), translocation sequencing (LAM PCR HTGTS), and
in vitro
genomic DNA digestion (Digenome-seq and SITE-Seq). Emphasis is placed on the specific modifications that give rise to the enhanced performance of contemporary techniques over their predecessors and the comparative performance of techniques for different applications. The clinical relevance of these techniques is discussed in the context of assessing the safety of novel CRISPR/Cas9 HIV-1 curative strategies. With the recent success of HIV-1 and SIV-1 viral suppression in humanized mice and non-human primates, respectively, using CRISPR/Cas9, rigorous exploration of potential off-target effects is of critical importance. Such analyses would benefit from the application of the techniques discussed in this review.
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Details
- Title
- Off-Target Analysis in Gene Editing and Applications for Clinical Translation of CRISPR/Cas9 in HIV-1 Therapy
- Creators
- Andrew Atkins - Drexel UniversityCheng-Han Chung - Drexel UniversityAlexander G. Allen - , , , , , , , ,Will Dampier - Drexel UniversityTheodore E. Gurrola - Drexel UniversityIlker K. Sariyer - Temple UniversityMichael R. Nonnemacher - Drexel UniversityBrian Wigdahl - Drexel University
- Publication Details
- Frontiers in genome editing, v 3, pp 673022-673022
- Publisher
- Frontiers Media S.A
- Grant note
- MH079785; MH092177; MH110360 / ;
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001011500300001
- Scopus ID
- 2-s2.0-85121473083
- Other Identifier
- 991020100194104721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biotechnology & Applied Microbiology
- Genetics & Heredity