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Research method

CRISPR-Cas9 Genome Editing

CRISPR in this library is two different objects that share a name. In bacteria it is an adaptive immune array of repeats and spacers; papers can catalogue those arrays without editing anything. In experimental cells and plants it is a programmable nuclease or RNA-targeting enzyme (Cas9, dCas9, Cas13a) used to cut, bind, or interfere with a chosen sequence. The student question 'what is CRISPR?' therefore has to ask which of those jobs the paper actually did.

Researchers reach for Cas enzymes when they need a targeted cut, a promoter pull-down, or sequence-specific viral interference; they reach for CRISPR-array scans when they are describing prokaryotic genomes. The method answers either 'what happens if we target this sequence?' or 'where are these arrays and what might they fold into?' Mixing those answers is the characteristic mistake this page exists to prevent. Native-array papers do not demonstrate genome editing; Cas-tool papers do not, by themselves, map every CRISPR locus in nature.

Evidence

What the evidence shows

Drawn from 9 studies in this library. Each finding starts with a plain-language takeaway, then the denser detail. Supports means evidence for a finding; Challenges means evidence against a stated position; Qualifies marks scope with a short note on each study’s contribution. Challenged positions are labeled — they are not findings.

  • Native CRISPR arrays can be studied as sequence and predicted RNA structure without any editing experiment. A scan of 439 genomes found 561 arrays in 195 genomes; some repeat clusters had consistently high folding potential, taken as support for RNA intermediates — computational structure, not a Cas9 knockout.

    1 study
    1. 1CRISPR repeats conserve RNA-like structure
  • Cas13a can be programmed as an antiviral in plants. Targeting different TuMV genomic regions reduced GFP and viral accumulation, showing sequence-specific RNA-virus interference rather than a DNA double-strand break. Guide choice still mattered, and the paper is not a field deployment against all RNA viruses.

    1 study
    1. 1Can Cas13a fight RNA viruses in plants?
  • Catalytically dead Cas9 can be used as a locus-specific hook. dCas9 chromatin immunoprecipitation (CasIP) in MDA-MB231 cells pulled RNAs at the FLI1 promoter and helped identify FECR1, a FLI1 exonic circRNA that activates FLI1 and promotes invasion — a dCas9 affinity experiment, not a knockout screen.

    1 study
    1. 1FLI1 circRNA FECR1 drives metastasis
  • Many papers in the CRISPR index mention CRISPR or Cas proteins in passing while the actual experiment is something else (APEX2 proximity labelling, pan-genome presence/absence, ChIP-seq of histone acylations, scRNA-seq of endoderm). Those hits show why a body-count lexicon over-recruits; they are not additional editing results.

    4 studies
    1. 1Mapping the faces of mitochondria and ER
    2. 2How open is the Listeria pan-genome?
    3. 3Histone acylations respond to plant stress
    4. 4What marks definitive endoderm progenitors in hESCs?

    Study comparison

    StudyRoleDesignNPopulationOutcome
    Mapping the faces of mitochondria and ER2017SupportsAnimal / in-vitroAPEX2 proximity labeling of cytosol-facing OMM and ER membranes in living HEK 293T cellsSILAC proteomic maps with two replicates per membrane — cell-resource studyHEK 293T cells expressing OMM/ERM APEX2 fusionsProteomes of cytosol-facing outer mitochondrial and ER membranes
    How open is the Listeria pan-genome?2013SupportsComputational / modellingExtended L. monocytogenes complete-genome set covering all serotypes for pan-genome analysisN=16 · 16 completely sequenced chromosomes (extended by 11 strains in this work)Listeria monocytogenes genomes across serotypesPan-genome stability and accessory-gene hotspot dynamics
    Histone acylations respond to plant stress2018SupportsAnimal / in-vitroMS and ChIP-seq mapping of histone Kbu/Kcr in rice vs H3K9ac under metabolic stressPlant chromatin proteomics/ChIP-seq study — no single primary analytic N in stored textRice (and related plants) under stress conditionsDistribution and stress dynamics of histone butyrylation/crotonylation
    What marks definitive endoderm progenitors in hESCs?2016SupportsAnimal / in-vitroscRNA-seq of H1/H9 progenitors and oxygen-condition tests during definitive endoderm differentiationN=1018 · 1,018 single cells analysed (including H1 n=212, H9 n=162, HFFs n=159)Human embryonic stem cells and lineage-specific progenitorsSingle-cell regulators and hypoxia effects on definitive endoderm differentiation

Open questions

Tensions and limits

Some items are genuine disagreements on the same question. Others mark different assays, populations, or outcomes — limits on how far one study travels — not a forced fight between papers.

  • Scope / different questions

    The strongest tension is naming. The 2007 array paper and the Listeria pan-genome treat CRISPR as a genomic feature of bacteria; the Cas13a and dCas9 papers treat CRISPR–Cas as a laboratory tool. Both usages are historically connected, but a finding about repeat RNA folding does not license a claim about editing a human promoter, and a CasIP result does not catalogue environmental CRISPR diversity.

    4 studies
    1. 1CRISPR repeats conserve RNA-like structure
    2. 2Can Cas13a fight RNA viruses in plants?
    3. 3FLI1 circRNA FECR1 drives metastasis
    4. 4How open is the Listeria pan-genome?

    Study comparison

    StudyRoleDesignNPopulationOutcome
    CRISPR repeats conserve RNA-like structure2007SupportsComputational / modellingGenome-wide CRISPR array detection and repeat secondary-structure scoringN=439 · 439 bacterial/archaeal genomes; 561 arrays in 195 genomesBacterial and archaeal sequenced genomesConserved CRISPR repeat sequence/structure features across clusters
    Can Cas13a fight RNA viruses in plants?2018SupportsAnimal / in-vitroProgrammed Cas13a targeting TuMV genomic regions in plantsPlant molecular interference assays — no single primary analytic N in stored textPlants infected with Turnip mosaic virus (TuMV)Cas13a-mediated reduction of viral GFP and accumulation
    FLI1 circRNA FECR1 drives metastasis2018SupportsAnimal / in-vitrodCas9 CasIP and functional assays of FECR1 circRNA in MDA-MB231 cellsCell-line mechanistic study; no single primary analytic N in stored textMDA-MB231 breast cancer cells (with tumor vs adjacent FLI1 context)FECR1 activation of FLI1 and invasive phenotypes
    How open is the Listeria pan-genome?2013SupportsComputational / modellingExtended L. monocytogenes complete-genome set covering all serotypes for pan-genome analysisN=16 · 16 completely sequenced chromosomes (extended by 11 strains in this work)Listeria monocytogenes genomes across serotypesPan-genome stability and accessory-gene hotspot dynamics
  • Scope / different questions

    Even among tool papers, the enzyme is not always Cas9 cutting DNA. Cas13a targets RNA viruses; dCas9 in CasIP binds without requiring a cut. Calling every experiment a 'CRISPR knockout' is false for this set.

    2 studies
    1. 1Can Cas13a fight RNA viruses in plants?
    2. 2FLI1 circRNA FECR1 drives metastasis

    Study comparison

    StudyRoleDesignNPopulationOutcome
    Can Cas13a fight RNA viruses in plants?2018SupportsAnimal / in-vitroProgrammed Cas13a targeting TuMV genomic regions in plantsPlant molecular interference assays — no single primary analytic N in stored textPlants infected with Turnip mosaic virus (TuMV)Cas13a-mediated reduction of viral GFP and accumulation
    FLI1 circRNA FECR1 drives metastasis2018SupportsAnimal / in-vitrodCas9 CasIP and functional assays of FECR1 circRNA in MDA-MB231 cellsCell-line mechanistic study; no single primary analytic N in stored textMDA-MB231 breast cancer cells (with tumor vs adjacent FLI1 context)FECR1 activation of FLI1 and invasive phenotypes

Common misconceptions

  • CRISPR in a paper always means the authors knocked out a gene with Cas9.

    In this library CRISPR often means a bacterial repeat-spacer array (439 genomes, 561 arrays) or a non-cutting tool (dCas9 CasIP, Cas13a RNA interference). Gene knockout and knockdown is a separate method page when loss-of-function is actually what was done.

    1. 1CRISPR repeats conserve RNA-like structure
    2. 2FLI1 circRNA FECR1 drives metastasis
    3. 3Can Cas13a fight RNA viruses in plants?
  • If Cas13a reduces viral GFP in plants, CRISPR is ready as a field antiviral for any RNA virus.

    Interference depended on which TuMV region was targeted; the paper does not demonstrate deployment across viruses or environments.

    1. 1Can Cas13a fight RNA viruses in plants?
  • Computational folding of CRISPR repeats proves those RNAs exist and function in the cell.

    The 2007 paper reports folding-potential scores across clusters as support for RNA intermediates, and explicitly is not direct RNA-structure proof for every array.

    1. 1CRISPR repeats conserve RNA-like structure

Exam-style questions

Short-answer questions that ask you to explain or compare, not recall.

A methods section says 'we analysed CRISPR.' List two experiments in this library that sentence could honestly describe, and one it should not.

It could mean scanning genomes for repeat-spacer arrays and scoring RNA-like folding, or programming Cas13a against TuMV, or pulling promoter-associated RNAs with dCas9. It should not be taken to mean an APEX2 mitochondrial-ER proteomic map or an scRNA-seq oxygen titration merely because those papers mention CRISPR in the text.

Compare Cas13a interference with dCas9 CasIP: what molecule is targeted, and is a double-strand DNA break required?

Cas13a is aimed at RNA virus genomes and reduces viral accumulation without being a DNA-cutting knockout. dCas9 in CasIP is used as a DNA-binding hook to recover RNAs at the FLI1 promoter; catalysis of a cut is not the point of that assay.

Why does finding 561 CRISPR arrays in 195 genomes not tell you what happens if you knock out FLI1 in a breast-cancer line?

That scan catalogues native prokaryotic arrays and predicted repeat structure. FLI1/FECR1 work uses dCas9 in human cells to study a circular RNA at a eukaryotic promoter. The shared acronym does not transfer the result.

How should a student use the gene-knockout-and-knockdown page together with this one?

Use this page when the paper's claim is about CRISPR arrays or Cas targeting. Use knockout/knockdown when the actual perturbation is loss of a gene product (shRNA, siRNA, a true knockout), which several papers in this index never do despite matching the CRISPR lexicon.

The studies

9 studies in this library bear on CRISPR-Cas9 Genome Editing, ordered by citations. The first 8 are shown.

Show 1 more studies

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