Evidence map›Paper›PMID 35414015›Full record

ArticleNature cell biology2022

Multiplexed genome regulation in vivo with hyper-efficient Cas12a.

Lucie Y Guo, Jing Bian, Alexander E Davis, Pingting Liu, Hannah R Kempton, Xiaowei Zhang, Augustine Chemparathy, Baokun Gu, Xueqiu Lin, Draven A Rane and 5 more

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

Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
7.9field-weighted citation impact, top 2% 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

74 citing papers in PubMed, 96 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Ratiometric transcriptional activation by protein degradation.bioRxiv : the preprint server for biology · 2026
    Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

14 more citing papers are in PubMed but not listed here.

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

15 authors at 3 institutions in 1 country.

Lucie Y Guo *Department of Bioengineering, Stanford University, Stanford, CA, USA. lucieguo@stanford.edu.ORCID http://orcid.org/0000-0003-1078-2504
Jing Bian *Department of Bioengineering, Stanford University, Stanford, CA, USA.
Alexander E DavisDepartment of Ophthalmology, Stanford University, Stanford, CA, USA.
Pingting LiuDepartment of Ophthalmology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1601-2818
Hannah R KemptonDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Xiaowei ZhangDepartment of Bioengineering, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-7749-4382
Augustine ChemparathyDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Baokun GuDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Xueqiu LinDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Draven A RaneDepartment of Bioengineering, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-9445-7260
Xiaoshu XuDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Ryan M JamiolkowskiDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Yang HuDepartment of Ophthalmology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-7980-1649
Sui WangDepartment of Ophthalmology, Stanford University, Stanford, CA, USA. suiwang@stanford.edu.ORCID http://orcid.org/0000-0003-1563-9117
Lei S QiDepartment of Bioengineering, Stanford University, Stanford, CA, USA. stanley.qi@stanford.edu.ORCID http://orcid.org/0000-0002-3965-3223
Stanford University · USStanford Medicine · USCardiovascular Institute of the South · US

Funding

Stanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI Jeffrey L Goldberg · 2017 to 2026
$8.0M
Engineering and Imaging 3D genome structure-function dynamics across time scalesU01DK127405 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI BLOBEL, GERD A, PHILLIPS-CREMINS, JENNIFER ELIZABETH · 2020 to 2024
$5.7M
Elucidating Neuron-Intrinsic Molecular Mechanisms of Optic Nerve RegenerationR01EY024932 · NEI · TEMPLE UNIV OF THE COMMONWEALTH · PI Yang Hu · 2015 to 2026
$4.8M
Neuroprotection by Modulating ER Stress in GlaucomaR01EY023295 · NEI · TEMPLE UNIV OF THE COMMONWEALTH · PI HU, YANG · 2013 to 2022
$3.8M
Circuit mechanisms for encoding naturalistic motion in the mammalian retinaR01NS109990 · NINDS · UNIVERSITY OF CHICAGO · PI WEI, WEI · 2018 to 2022
$3.3M
Optineurin dysfunction induces neurodegeneration in normal tension glaucoma by a novel molecular mechanismR01EY032518 · NEI · STANFORD UNIVERSITY · PI Yang Hu · 2022 to 2026
$2.7M
Stanford Neurosurgery Resident Research Education ProgramR25NS065741 · NINDS · STANFORD UNIVERSITY · PI HAYDEN GEPHART, MELANIE, PORTER, BRENDA ELAINE · 2009 to 2022
$2.0M
Mechanisms regulating the plasticity of postmitotic cells in mammalian retinaR01EY032585 · NEI · STANFORD UNIVERSITY · PI WANG, SUI · 2021 to 2025
$2.0M
Developing Novel Neuroprotective Strategies for EAE/Optic NeuritisR01EY028106 · NEI · STANFORD UNIVERSITY · PI HU, YANG · 2018 to 2021
$1.9M
Vision Research Training ProgramT32EY020485 · NEI · STANFORD UNIVERSITY · PI BARRES, BEN A, LIAO, YAPING JOYCE · 2010 to 2014
$795k
NEI NIH HHS P30 EY026877NEI NIH HHS R01 EY023295NEI NIH HHS R01 EY024932NEI NIH HHS R01 EY028106NEI NIH HHS R01 EY032518NEI NIH HHS R01 EY032585NEI NIH HHS T32 EY020485NIDDK NIH HHS U01 DK127405NINDS NIH HHS R01 NS109990NINDS NIH HHS R25 NS065741
6 · The paper itself

Abstract

Multiplexed modulation of endogenous genes is crucial for sophisticated gene therapy and cell engineering. CRISPR-Cas12a systems enable versatile multiple-genomic-loci targeting by processing numerous CRISPR RNAs (crRNAs) from a single transcript; however, their low efficiency has hindered in vivo applications. Through structure-guided protein engineering, we developed a hyper-efficient Lachnospiraceae bacterium Cas12a variant, termed hyperCas12a, with its catalytically dead version hyperdCas12a showing significantly enhanced efficacy for gene activation, particularly at low concentrations of crRNA. We demonstrate that hyperdCas12a has comparable off-target effects compared with the wild-type system and exhibits enhanced activity for gene editing and repression. Delivery of the hyperdCas12a activator and a single crRNA array simultaneously activating the endogenous Oct4, Sox2 and Klf4 genes in the retina of post-natal mice alters the differentiation of retinal progenitor cells. The hyperCas12a system offers a versatile in vivo tool for a broad range of gene-modulation and gene-therapy applications.

Indexed as

CRISPR-Associated ProteinsAnimalsCRISPR-Cas SystemsGene EditingMiceRNACRISPR-Associated ProteinsRNA

Identifiers

PMID35414015
PMCPMC9035114
OpenAlexW4223496046

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.