Cited by 3,153CRISPR and Genetic EngineeringRNA regulation and diseaseRNA Interference and Gene Delivery

CRISPR-Cas systems for editing, regulating and targeting genomes

Open access
Sander, Jeffry D, Joung, J Keith·2014·Nature Biotechnology

Abstract

Targeted genome editing using engineered nucleases has rapidly gone from being a niche technology to a mainstream method used by many biological researchers. This widespread adoption has been largely fueled by the emergence of the clustered, regularly interspaced, short palindromic repeat (CRISPR) technology, an important new approach for generating RNA-guided nucleases, such as Cas9, with customizable specificities. Genome editing mediated by these nucleases has been used to rapidly, easily and efficiently modify endogenous genes in a wide variety of biomedically important cell types and in organisms that have traditionally been challenging to manipulate genetically. Furthermore, a modified version of the CRISPR-Cas9 system has been developed to recruit heterologous domains that can regulate endogenous gene expression or label specific genomic loci in living cells. Although the genome-wide specificities of CRISPR-Cas9 systems remain to be fully defined, the power of these systems to perform targeted, highly efficient alterations of genome sequence and gene expression will undoubtedly transform biological research and spur the development of novel molecular therapeutics for human disease.

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  • CRISPRs are related to the adaptive immunity system that has been widely identified and characterized in many archaea and bacteria.

    “CRISPRs, a type of important repeat elements, are related to the adaptive immunity system that has been widely identified and characterized in many archaea and bacteria.63 , 64”

    From Whole genomic DNA sequencing and comparative genomic analysis of<i>Arthrospira platensis</i>: high genome plasticity and genetic diversity (2016) · cites this paper as [64]

    The section “From bacterial CRISPR-Cas immune system to engineered RNA-guided nucleases” describes CRISPR systems as immune mechanisms used by many bacteria and explains their repeat arrays. The paper’s References include works on CRISPR immunity in archaea, but the discussion does not establish that these systems have been widely identified and characterized in many archaea. (LLM, conf=0.82)

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  • CRISPR technology has drawbacks including Cas9 off-target activity, cost, and a labor-intensive process of guide RNA design, viral packaging and infection, isolation of single cells, expansion of clones, and verification of correct targeting.

    “While complete gene knockout is often preferred, there are some drawbacks of CRISPR technology including Cas9 off-target activity [46], as well as the cost and labor-intensive process of guide RNA design, viral packaging and infection, isolation of single cells, expansion of clones, and verification of correct targeting [47].”

    From Regulation of Enterocyte Brush Border Membrane Primary Na-Absorptive Transporters in Human Intestinal Organoid-Derived Monolayers (2024) · cites this paper as [46]

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  • Targeted genome editing approaches such as CRISPR-Cas9 may be used to actively introduce highly specific changes in the genome instead of screening for random changes.

    “Additionally, targeted genome editing approaches such as CRISPR-Cas9 and related technologies may be used to actively introduce highly specific changes in the genome instead of screening for random changes (reviewed in Sander and Joung, 2014).”

    From Shaping plant architecture (2015) · cites this paper as Sander and Joung, 2014

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1 of the 102 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. [55]Hsu PD DNA targeting specificity of RNA-guided Cas9 nucleases Nat Biotechnol 2013 31 827 832 23873081 PMC3969858
  2. [58]Pattanayak V High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity Nat Biotechnol 2013 PMC3782611 23934178
  3. [89]Wolfe SA Nekludova L Pabo CO DNA recognition by Cys2His2 zinc finger proteins Annu Rev Biophys Biomol Struct 2000 29 183 212 10940247

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Authors
Sander, J. D., & Joung, J. K.
Affiliations
Harvard University (US)
Corresponding author
Joung, J Keith
Venue
Nature Biotechnology
Published
2014-03-02
Volume
32
Issue
4
Pages
347-355
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2039705224
Cited by
3,153
References
102
Citations by year
2026: 79 · 2025: 153 · 2024: 167 · 2023: 166 · 2022: 233 · 2021: 225 · 2020: 271 · 2019: 298 · 2018: 379 · 2017: 368 · 2016: 384 · 2015: 300 · 2014: 124 · 2013: 2 · 2012: 1
FWCI
36.95
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of General Medical Sciences (DP1GM105378, R01GM088040)
  • National Center for Chronic Disease Prevention and Health Promotion (DP1 GM105378)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
CRISPR/Cas9, genome editing, RNA-guided nucleases, engineered nucleases, gene expression regulation, targeted mutagenesis, molecular therapeutics
MeSH terms
Animals, Genetic Engineering, Humans, Rabbits, Genomics, Mice, Rats, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems

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