Evidence map›Paper›PMID 31570731›Full record

ArticleNature communications2019

High levels of AAV vector integration into CRISPR-induced DNA breaks.

Killian S Hanlon, Benjamin P Kleinstiver, Sara P Garcia, Mikołaj P Zaborowski, Adrienn Volak, Stefan E Spirig, Alissa Muller, Alexander A Sousa, Shengdar Q Tsai, Niclas E Bengtsson and 9 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 286 papers.

0numbers the graph read from it
0cells of the map it votes in
286citing papers in PubMed
15.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

286 citing papers in PubMed, 414 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Chemically modified CRISPR enzymes for multi-organ genome editingbioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. SORT LNPs encapsulating Cas9 mRNA achieve efficient editing in skeletal muscle in a dystrophic mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  17. In vivo systematic detection of the outcomes of CRISPR-Cas9-mediated DNA repair in skeletal muscle stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  18. Review
  19. Article
  20. Article

226 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 4 countries.

Killian S HanlonDepartment of Neurobiology, Harvard Medical School, Boston, MA, 02115, USA.
Benjamin P KleinstiverCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5469-0655
Sara P GarciaDepartment of Pathology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3312-6454
Mikołaj P ZaborowskiMolecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.ORCID http://orcid.org/0000-0002-4400-6688
Adrienn VolakMolecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Stefan E SpirigInstitute of Molecular and Clinical Ophthalmology Basel, 4031, Basel, Switzerland.
Alissa MullerInstitute of Molecular and Clinical Ophthalmology Basel, 4031, Basel, Switzerland.
Alexander A SousaMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Shengdar Q TsaiDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0001-9161-3993
Niclas E BengtssonDepartment of Neurology, University of Washington, Seattle, WA, 98195, USA.
Camilla LöövUppsala University, Department of Public Health and Caring Sciences, Geriatrics, Uppsala, Sweden.
Martin IngelssonUppsala University, Department of Public Health and Caring Sciences, Geriatrics, Uppsala, Sweden.
Jeffrey S ChamberlainDepartment of Neurology, University of Washington, Seattle, WA, 98195, USA.
David P CoreyDepartment of Neurobiology, Harvard Medical School, Boston, MA, 02115, USA.
Martin J AryeeDepartment of Pathology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6848-1344
J Keith JoungDepartment of Pathology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5630-5645
Xandra O BreakefieldMolecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Casey A MaguireMolecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA. cmaguire@mgh.harvard.edu.
Bence GyörgyDepartment of Neurobiology, Harvard Medical School, Boston, MA, 02115, USA. bence.gyoergy@iob.ch.ORCID http://orcid.org/0000-0003-0766-6246
Harvard University · USInstitute of Molecular and Clinical Ophthalmology Basel · CHMassachusetts General Hospital · USUniversity of Washington · USUppsala University · SEPoznan University of Medical Sciences · PLSt. Jude Children's Research Hospital · US

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Assembly of the Dystrophin-Glycoprotein ComplexR01AR044533 · NIAMS · UNIVERSITY OF WASHINGTON · PI CHAMBERLAIN, JEFFREY S · 1997 to 2021
$8.9M
Evolution, Optimization, and Application of Genome Editing TechnologiesR35GM118158 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2016 to 2023
$4.7M
Enhanced gene delivery for CNS and sensory disordersR01DC017117 · NIDCD · MASSACHUSETTS GENERAL HOSPITAL · PI MAGUIRE, CASEY A · 2019 to 2023
$1.8M
Optimizing Cancer Immunotherapy Safety and Efficacy using Genome EditingR00CA218870 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI KLEINSTIVER, BENJAMIN PETER · 2018 to 2020
$730k
NCI NIH HHS R00 CA218870NHGRI NIH HHS RM1 HG009490NIAMS NIH HHS R01 AR044533NIDCD NIH HHS R01 DC017117NIGMS NIH HHS R35 GM118158
6 · The paper itself

Abstract

Adeno-associated virus (AAV) vectors have shown promising results in preclinical models, but the genomic consequences of transduction with AAV vectors encoding CRISPR-Cas nucleases is still being examined. In this study, we observe high levels of AAV integration (up to 47%) into Cas9-induced double-strand breaks (DSBs) in therapeutically relevant genes in cultured murine neurons, mouse brain, muscle and cochlea. Genome-wide AAV mapping in mouse brain shows no overall increase of AAV integration except at the CRISPR/Cas9 target site. To allow detailed characterization of integration events we engineer a miniature AAV encoding a 465 bp lambda bacteriophage DNA (AAV-λ465), enabling sequencing of the entire integrated vector genome. The integration profile of AAV-465λ in cultured cells display both full-length and fragmented AAV genomes at Cas9 on-target sites. Our data indicate that AAV integration should be recognized as a common outcome for applications that utilize AAV for genome editing.

Indexed as

CRISPR-Cas SystemsDNA BreaksGenetic VectorsAnimalsBacteriophage lambdaBrainCell LineChromosome MappingClustered Regularly Interspaced Short Palindromic RepeatsCochleaDependovirusEndonucleasesGene EditingGene TargetingGenetic TherapyGenomeEndonucleases

Identifiers

PMID31570731
PMCPMC6769011
OpenAlexW2976425815

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.