Evidence map›Paper›PMID 34162850›Full record

ArticleNature communications2021

AsCas12a ultra nuclease facilitates the rapid generation of therapeutic cell medicines.

Liyang Zhang, John A Zuris, Ramya Viswanathan, Jasmine N Edelstein, Rolf Turk, Bernice Thommandru, H Tomas Rube, Steve E Glenn, Michael A Collingwood, Nicole M Bode and 14 more

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing 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

107 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Efficient CRISPR-Cas RNP-based gene targeting of human AT2 cells.American journal of respiratory cell and molecular biology · 2026
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Nonclinical evaluation of renizgamglogene autogedtemcel for SCD and TDT.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Liyang Zhang *Integrated DNA Technologies, Inc, Coralville, IA, USA.
John A Zuris *Editas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Ramya Viswanathan *Editas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Jasmine N Edelstein *Editas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Rolf Turk *Integrated DNA Technologies, Inc, Coralville, IA, USA.ORCID http://orcid.org/0000-0003-1283-9594
Bernice Thommandru *Integrated DNA Technologies, Inc, Coralville, IA, USA.
H Tomas Rube *University of California - Merced, 5200 Lake Rd, Merced, CA, USA.
Steve E GlennIntegrated DNA Technologies, Inc, Coralville, IA, USA.
Michael A CollingwoodIntegrated DNA Technologies, Inc, Coralville, IA, USA.
Nicole M BodeIntegrated DNA Technologies, Inc, Coralville, IA, USA.ORCID http://orcid.org/0000-0001-7209-303X
Sarah F BeaudoinIntegrated DNA Technologies, Inc, Coralville, IA, USA.ORCID http://orcid.org/0000-0001-9337-3022
Swarali LeleEditas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Sean N ScottEditas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Kevin M WaskoEditas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Steven SextonEditas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Christopher M BorgesEditas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Mollie S SchubertIntegrated DNA Technologies, Inc, Coralville, IA, USA.
Gavin L KurganIntegrated DNA Technologies, Inc, Coralville, IA, USA.ORCID http://orcid.org/0000-0002-4047-1427
Matthew S McNeillIntegrated DNA Technologies, Inc, Coralville, IA, USA.ORCID http://orcid.org/0000-0002-8737-785X
Cecilia A FernandezEditas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Vic E MyerEditas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Richard A MorganEditas Medicine Inc, 11 Hurley St, Cambridge, MA, USA.
Mark A BehlkeIntegrated DNA Technologies, Inc, Coralville, IA, USA. mbehlke@idtdna.com.ORCID http://orcid.org/0000-0002-4218-857X
Christopher A VakulskasIntegrated DNA Technologies, Inc, Coralville, IA, USA. cvakulskas@idtdna.com.ORCID http://orcid.org/0000-0001-8510-4332

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Though AsCas12a fills a crucial gap in the current genome editing toolbox, it exhibits relatively poor editing efficiency, restricting its overall utility. Here we isolate an engineered variant, "AsCas12a Ultra", that increased editing efficiency to nearly 100% at all sites examined in HSPCs, iPSCs, T cells, and NK cells. We show that AsCas12a Ultra maintains high on-target specificity thereby mitigating the risk for off-target editing and making it ideal for complex therapeutic genome editing applications. We achieved simultaneous targeting of three clinically relevant genes in T cells at >90% efficiency and demonstrated transgene knock-in efficiencies of up to 60%. We demonstrate site-specific knock-in of a CAR in NK cells, which afforded enhanced anti-tumor NK cell recognition, potentially enabling the next generation of allogeneic cell-based therapies in oncology. AsCas12a Ultra is an advanced CRISPR nuclease with significant advantages in basic research and in the production of gene edited cell medicines.

Indexed as

CRISPR-Cas SystemsAcidaminococcusBacterial ProteinsCells, CulturedCRISPR-Associated ProteinsEndonucleasesGene EditingHEK293 CellsHematopoietic Stem CellsHumansInduced Pluripotent Stem CellsJurkat CellsKiller Cells, NaturalReproducibility of ResultsT-LymphocytesBacterial ProteinsCRISPR-Associated ProteinsEndonucleases

Identifiers

PMID34162850
PMCPMC8222333

What OpenQuestion holds

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LicenceCC BY
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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.