Evidence map›Paper›PMID 36527789›Full record

ArticleBiomaterials2023

Efficient in vivo neuronal genome editing in the mouse brain using nanocapsules containing CRISPR-Cas9 ribonucleoproteins.

Jeanette M Metzger, Yuyuan Wang, Samuel S Neuman, Kathy J Snow, Stephen A Murray, Cathleen M Lutz, Viktoriya Bondarenko, Jesi Felton, Kirstan Gimse, Ruosen Xie and 9 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.3field-weighted citation impact, top 10% 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

21 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  3. International journal of biological sciences · 2026
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  18. Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
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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 4 institutions in 1 country.

Jeanette M MetzgerWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Yuyuan WangDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Samuel S NeumanWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Kathy J SnowThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Stephen A MurrayThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Cathleen M LutzThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Viktoriya BondarenkoWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Jesi FeltonWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Kirstan GimseDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Ruosen XieDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Dongdong LiDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Yi ZhaoDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Matthew T FlowersWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Heather A SimmonsWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Subhojit RoyDepartments of Pathology and Neuroscience, University of California-San Diego, San Diego, CA, 92093, USA.
Krishanu SahaDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Jon E LevineWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Marina E EmborgWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, 53715, USA. Electronic address: emborg@wisc.edu.
Shaoqin GongDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA. Electronic address: shaoqingong@wisc.edu.
University of Wisconsin–Madison · USJackson Laboratory · USUniversity of California San Diego · USUniversity of Wisconsin System · US

Funding

WNPRC Supplemental Request for Nonhuman Primate Enclosures to Equip HIV/AIDS-Related Research FacilitiesP51OD011106 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI Dorota A. Grejner-Brzezinska · 2012 to 2026
$150.7M
Institutional Training in the Genomic SciencesT32HG002760 · NHGRI · UNIVERSITY OF WISCONSIN-MADISON · PI Qiongshi Lu · 2003 to 2026
$17.7M
The Jackson Laboratory Gene Editing Testing Center (JAX-GETC)U42OD026635 · OD · JACKSON LABORATORY · PI MURRAY, STEPHEN A · 2018 to 2022
$4.6M
Enabling Nanoplatforms for Targeted in vivo Delivery of CRISPR/Cas9 Ribonucleoproteins in the BrainUH3NS111688 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI EMBORG, MARINA, GONG, SHAOQIN - · 2021 to 2022
$2.4M
Enabling Nanoplatforms for Targeted in vivo Delivery of CRISPR/Cas9 Ribonucleoproteins in the BrainUG3NS111688 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI EMBORG, MARINA, GONG, SHAOQIN - · 2018 to 2020
$2.3M
An Upright Multiphoton Microscopy System to Support the Biomedical SciencesS10OD025040 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI AUDHYA, ANJON · 2018 to 2018
$597k
NHGRI NIH HHS T32 HG002760NIH HHS P51 OD011106NIH HHS S10 OD025040NIH HHS U42 OD026635NINDS NIH HHS UG3 NS111688NINDS NIH HHS UH3 NS111688
6 · The paper itself

Abstract

Genome editing of somatic cells via clustered regularly interspaced short palindromic repeats (CRISPR) offers promise for new therapeutics to treat a variety of genetic disorders, including neurological diseases. However, the dense and complex parenchyma of the brain and the post-mitotic state of neurons make efficient genome editing challenging. In vivo delivery systems for CRISPR-Cas proteins and single guide RNA (sgRNA) include both viral vectors and non-viral strategies, each presenting different advantages and disadvantages for clinical application. We developed non-viral and biodegradable PEGylated nanocapsules (NCs) that deliver preassembled Cas9-sgRNA ribonucleoproteins (RNPs). Here, we show that the RNP NCs led to robust genome editing in neurons following intracerebral injection into the healthy mouse striatum. Genome editing was predominantly observed in medium spiny neurons (>80%), with occasional editing in cholinergic, calretinin, and parvalbumin interneurons. Glial activation was minimal and was localized along the needle tract. Our results demonstrate that the RNP NCs are capable of safe and efficient neuronal genome editing in vivo.

Indexed as

Gene EditingNanocapsulesAnimalsBrainCRISPR-Cas SystemsMiceNeuronsRibonucleoproteinsNanocapsulesRibonucleoproteinsBrainCRISPRGenome editingNanocapsuleNanoparticleNeuron

Identifiers

PMID36527789
PMCPMC9868115
OpenAlexW4311771185

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.