Evidence map›Paper›PMID 41673027›Full record

ArticleNature communications2026

dHyperCas12a enables multiplexed CRISPRi screens.

Schuyler M Melore, Christian D McRoberts Amador, Marisa C Hamilton, Charles A Gersbach, Timothy E Reddy

Abstract read
In one paragraph

Article in Nature communications, 2026. 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. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Schuyler M MeloreUniversity Program in Genetics & Genomics, Duke University, Durham, NC, USA.ORCID 0000-0002-0694-6388
Christian D McRoberts Amador *Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA.ORCID 0000-0001-5595-1450
Marisa C Hamilton *University Program in Genetics & Genomics, Duke University, Durham, NC, USA.
Charles A GersbachUniversity Program in Genetics & Genomics, Duke University, Durham, NC, USA.ORCID 0000-0003-1478-4013
Timothy E ReddyUniversity Program in Genetics & Genomics, Duke University, Durham, NC, USA. treddy@altius.org.ORCID 0000-0002-7629-061X

Funding

The Duke FUNCTION Center: Pioneering the comprehensive identification of combinatorial noncoding causes of diseaseRM1HG011123 · NHGRI · DUKE UNIVERSITY · PI GREGORY E CRAWFORD, Raluca Gordan · 2020 to 2026
$21.9M
High-Throughput Functional Annotation of Gene Regulatory Elements and Variants Critical to Complex Cellular PhenotypesUM1HG012053 · NHGRI · DUKE UNIVERSITY · PI GREGORY E CRAWFORD, Charles A. Gersbach · 2021 to 2026
$10.7M
Epigenetic Programming of T Cells for Enhanced Cellular ImmunotherapyR01CA289574 · NCI · DUKE UNIVERSITY · PI Charles A. Gersbach · 2024 to 2026
$1.7M
Epigenome Editing Technologies for Treating Diverse DiseaseU01AI146356 · NIAID · DUKE UNIVERSITY · PI GERSBACH, CHARLES A. · 2019 to 2022
$1.6M
NCI NIH HHS R01 CA289574NHGRI NIH HHS RM1 HG011123NHGRI NIH HHS UM1 HG012053NIAID NIH HHS U01 AI146356
6 · The paper itself

Abstract

Interactions between genes or cis-regulatory elements (CREs) underlie many biological processes. High-throughput CRISPR screens have allowed researchers to assess the impact of activation or repression of gene and regulatory elements on many phenotypes. However, assessment of interactions between those genes or elements remains limited. To enable efficient highly-multiplexed control of regulatory element activity, we combine a hyper-efficient version of Lachnospiraceae bacterium dCas12a (dHyperLbCas12a) with RNA Polymerase II expression of long CRISPR RNA (crRNA) arrays. We demonstrate this system with several activation and repression domains, in cultured primary immune cells, and to differentiate induced pluripotent stem cells. We also develop approaches to use dCas12a for simultaneous activation and repression. Lastly, we demonstrate that dHyperLbCas12a effectors can be used to dissect the independent and combinatorial contributions of CREs to gene expression. These tools create possibilities for highly multiplexed control of gene expression in many biological systems.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsAnimalsHumansInduced Pluripotent Stem CellsRNA Polymerase IIRNA Polymerase II

Identifiers

PMID41673027
PMCPMC13004945

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.