Evidence map›Paper›PMID 40847019›Full record

ArticleNature neuroscience2025

CRISPR screening by AAV episome-sequencing (CrAAVe-seq): a scalable cell-type-specific in vivo platform uncovers neuronal essential genes.

Biswarathan Ramani, Indigo V L Rose, Noam Teyssier, Andrew Pan, Spencer Danner-Bocks, Tanya Sanghal, Lin Yadanar, Ruilin Tian, Keran Ma, Jorge J Palop and 1 more

Abstract read
In one paragraph

Article in Nature neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed.

  1. Review
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  13. Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026
    Review
  14. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Biswarathan Ramani *Institute for Neurodegenerative Diseases; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9723-5599
Indigo V L Rose *Institute for Neurodegenerative Diseases; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0491-1269
Noam TeyssierInstitute for Neurodegenerative Diseases; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Andrew PanInstitute for Neurodegenerative Diseases; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Spencer Danner-BocksInstitute for Neurodegenerative Diseases; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0009-1435-7354
Tanya SanghalInstitute for Neurodegenerative Diseases; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Lin YadanarInstitute for Neurodegenerative Diseases; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Ruilin TianInstitute for Neurodegenerative Diseases; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-7680-6682
Keran MaGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Jorge J PalopGladstone Institute of Neurological Disease, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6086-1070
Martin KampmannInstitute for Neurodegenerative Diseases; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. martin.kampmann@ucsf.edu.ORCID http://orcid.org/0000-0002-3819-7019

Funding

NINDS Research Education Programs for Residents and Fellows in Neurology, Neurosurgery, Neuropathology, Neuroradiology and Emergency Medicine (R25)R25NS070680 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOSEPHSON, SCOTT ANDREW · 2010 to 2023
$6.8M
Optogenetic dissection of cellular and circuit mechanisms of network dysfunction and amyloid deposition in mouse models of Alzheimer's disease in vivoRF1AG062234 · NIA · J. DAVID GLADSTONE INSTITUTES · PI PALOP, JORGE J · 2018 to 2021
$3.8M
Predoctoral Training in NeurobiologyT32NS115706 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAMUEL JEREMY PLEASURE · 2020 to 2026
$3.4M
Molecular mechanisms of selective vulnerability of neurons to tauopathyR01AG082141 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CARLO L CONDELLO, Martin Kampmann · 2023 to 2026
$3.0M
Post Baccalaureate Research Opportunity To Promote Equity In Learning (PROPEL).R25GM144250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Ryan D. Hernandez, Todd Nystul · 2022 to 2026
$1.8M
Unraveling the role of the molecular co-chaperone DNAJC7 in protein homeostasis and neurodegenerationK08NS133300 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Biswarathan Ramani · 2024 to 2026
$587k
Functional Alterations of Parvalbumin Interneurons Contributing to Abnormal Network Activity in Alzheimer's Disease Mouse ModelsK99AG062776 · NIA · J. DAVID GLADSTONE INSTITUTES · PI MA, KERAN · 2019 to 2021
$393k
California Institute for Regenerative Medicine (CIRM) EDUC4-12812Larry L. Hillblom Foundation (Larry L. Hillblom Foundation, Inc.) UCSF Hillblom/BARI Graduate Fellowship AwardNIA NIH HHS K99 AG062776NIA NIH HHS R01 AG082141NIA NIH HHS RF1 AG062234NIGMS NIH HHS R25 GM144250NINDS NIH HHS K08 NS133300NINDS NIH HHS R25 NS070680NINDS NIH HHS T32 NS115706
6 · The paper itself

Abstract

There is a substantial need for scalable CRISPR-based genetic screening methods that can be applied in mammalian tissues in vivo while enabling cell-type-specific analysis. Here we developed an adeno-associated virus (AAV)-based CRISPR screening platform, CrAAVe-seq, that incorporates a Cre-sensitive sgRNA construct for pooled screening within targeted cell populations in mouse tissues. We used this approach to screen two large sgRNA libraries, which collectively target over 5,000 genes, in mouse brains and uncovered genes essential for neuronal survival, of which we validated Rabggta and Hspa5. We highlight the reproducibility and scalability of the platform and show that it is sufficiently sensitive for screening in a restricted subset of neurons. We systematically characterize the impact of sgRNA library size, mouse cohort size, the size of the targeted cell population, viral titer, and coinfection rate on screen performance to establish general guidelines for large-scale in vivo screens.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsDependovirusGenes, EssentialGenetic TestingNeuronsAnimalsHumansMiceMice, Inbred C57BL

Identifiers

PMID40847019
PMCPMC12497649

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.