Evidence map›Paper›PMID 37719144›Full record

ArticleCell genomics2023

Optimization of Cas12a for multiplexed genome-scale transcriptional activation.

Audrey L Griffith, Fengyi Zheng, Abby V McGee, Nathan W Miller, Zsofia M Szegletes, Ganna Reint, Fabian Gademann, Ifunanya Nwolah, Mudra Hegde, Yanjing V Liu and 2 more

Abstract read
In one paragraph

Article in Cell genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. HyperCas12a enables multiplexed CRISPRi screens.bioRxiv : the preprint server for biology · 2025
    Article
  11. Review
  12. Article
  13. Article
  14. Gene Therapy Techniques and Delivery Methods (Review).Sovremennye tekhnologii v meditsine · 2025
    Review
  15. Article
  16. Article
  17. Review
  18. Article
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

12 authors.

Audrey L GriffithGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
Fengyi ZhengGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
Abby V McGeeGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
Nathan W MillerGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
Zsofia M SzegletesGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
Ganna ReintGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
Fabian GademannGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
Ifunanya NwolahGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
Mudra HegdeGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
Yanjing V LiuGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
Amy GoodaleGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.
John G DoenchGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St., Cambridge, MA 02142, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cas12a CRISPR technology, unlike Cas9, allows for facile multiplexing of guide RNAs from a single transcript, simplifying combinatorial perturbations. While Cas12a has been implemented for multiplexed knockout genetic screens, it has yet to be optimized for CRISPR activation (CRISPRa) screens in human cells. Here, we develop a new Cas12a-based transactivation domain (TAD) recruitment system using the ALFA nanobody and demonstrate simultaneous activation of up to four genes. We screen a genome-wide library to identify modulators of growth and MEK inhibition, and we compare these results with those obtained with open reading frame (ORF) overexpression and Cas9-based CRISPRa. We find that the activity of multiplexed arrays is largely predictable from the best-performing guide and provide criteria for selecting active guides. We anticipate that these results will greatly accelerate the exploration of gene function and combinatorial phenotypes at scale.

Indexed as

Cas12aCRISPR activationfunctional genomicsgenetic screens

Identifiers

PMID37719144
PMCPMC10504673

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.