Evidence map›Paper›PMID 38091988›Full record

ArticleCell reports methods2024

Parallelized engineering of mutational models using piggyBac transposon delivery of CRISPR libraries.

Xander Nuttle, Nicholas D Burt, Benjamin Currall, Mariana Moysés-Oliveira, Kiana Mohajeri, Riya Bhavsar, Diane Lucente, Rachita Yadav, Derek J C Tai, James F Gusella and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports methods, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Dual-line Genome-scale CRISPR Screening Enables Robust Target Gene Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Article
  3. Clinical,medRxiv : the preprint server for health sciences · 2026
    Article
  4. Review
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

11 authors.

Xander NuttleCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. Electronic address: anuttle@mgh.harvard.edu.
Nicholas D BurtCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Benjamin CurrallCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Mariana Moysés-OliveiraCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Kiana MohajeriCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; PhD program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA.
Riya BhavsarCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Diane LucenteCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Rachita YadavCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Derek J C TaiCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
James F GusellaCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA.
Michael E TalkowskiCenter for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. Electronic address: mtalkowski@mgh.harvard.edu.

Funding

The Massachusetts General Hospital Harvard Center for Reproductive MedicineP50HD104224 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI SEMINARA, STEPHANIE BETH · 2021 to 2025
$7.8M
Disease-Modifying Genes in Huntington's DiseaseR01NS091161 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI JAMES F GUSELLA · 2015 to 2026
$7.2M
Functional convergence following disruption of diverse genes associated with neurodevelopmental disordersR01MH123155 · NIMH · YALE UNIVERSITY · PI BRENNAND, KRISTEN JENNIFER, RUDERFER, DOUGLAS · 2021 to 2025
$4.1M
Molecular mechanisms and genetic drivers of reciprocal genomic disordersR01HD096326 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2018 to 2022
$3.5M
Dissecting recurrent microdeletion syndromes using dual-guide genome editingR01NS093200 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI GUSELLA, JAMES F · 2015 to 2019
$2.9M
Modeling Reciprocal Genomic Disorders in Neuronal Cells and Cerebral OrganoidsK99MH121577 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI NUTTLE, XANDER · 2021 to 2022
$221k
Deconstructing Reciprocal Genomic Disorders by Integration of Genome Engineering and Cellular ModelingF32MH115614 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI NUTTLE, XANDER · 2017 to 2018
$123k
NICHD NIH HHS P50 HD104224NICHD NIH HHS R01 HD096326NIMH NIH HHS F32 MH115614NIMH NIH HHS K99 MH121577NIMH NIH HHS R01 MH123155NINDS NIH HHS R01 NS091161NINDS NIH HHS R01 NS093200
6 · The paper itself

Abstract

New technologies and large-cohort studies have enabled novel variant discovery and association at unprecedented scale, yet functional characterization of these variants remains paramount to deciphering disease mechanisms. Approaches that facilitate parallelized genome editing of cells of interest or induced pluripotent stem cells (iPSCs) have become critical tools toward this goal. Here, we developed an approach that incorporates libraries of CRISPR-Cas9 guide RNAs (gRNAs) together with inducible Cas9 into a piggyBac (PB) transposon system to engineer dozens to hundreds of genomic variants in parallel against isogenic cellular backgrounds. This method empowers loss-of-function (LoF) studies through the introduction of insertions or deletions (indels) and copy-number variants (CNVs), though generating specific nucleotide changes is possible with prime editing. The ability to rapidly establish high-quality mutational models at scale will facilitate the development of isogenic cellular collections and catalyze comparative functional genomic studies investigating the roles of hundreds of genes and mutations in development and disease.

Indexed as

CRISPR-Cas SystemsInduced Pluripotent Stem CellsGene EditingGenomicsHumansMutationallelic seriesCP: GeneticsCP: Stem cellCRISPRfunctional genomicsgenome editinggenome engineeringgRNA libraryinduced pluripotent stem cellsmutational modelingpiggyBac transposon

Identifiers

PMID38091988
PMCPMC10831954

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.