Evidence map›Paper›PMID 32792475›Full record

ArticleNature communications2020

Engineering designer beta cells with a CRISPR-Cas9 conjugation platform.

Donghyun Lim, Vedagopuram Sreekanth, Kurt J Cox, Benjamin K Law, Bridget K Wagner, Jeffrey M Karp, Amit Choudhary

Abstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing 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

33 citing papers in PubMed.

  1. Wheat's Up with CRISPR-Cas-Current Advances, Obstacles and Perspectives.International journal of molecular sciences · 2026
    Review
  2. Review
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  4. eVLP-Mediated Cas9 Delivery for Preventing IBMIR in Islet Transplantation.Small (Weinheim an der Bergstrasse, Germany) · 2026
    Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
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  13. Article
  14. The application of metaverse in healthcare.Frontiers in public health · 2024
    Review
  15. Article
  16. Article
  17. Review
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  19. Article
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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

7 authors.

Donghyun LimChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Vedagopuram SreekanthChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Kurt J CoxChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Benjamin K LawChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Bridget K WagnerChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Jeffrey M KarpEngineering in Medicine, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-4752-7374
Amit ChoudharyChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. achoudhary@bwh.harvard.edu.ORCID http://orcid.org/0000-0002-8437-0150

Funding

Development of small molecule-based methods for targeted cargo delivery to beta cellsUC4DK116255 · NIDDK · BROAD INSTITUTE, INC. · PI CHOUDHARY, AMIT, KULKARNI, ROHIT N. · 2017 to 2017
$2.7M
Leveraging snakes' extreme physiology to modulate human beta-cell functionR01DK113597 · NIDDK · BROAD INSTITUTE, INC. · PI CHOUDHARY, AMIT, SECOR, STEPHEN M · 2016 to 2020
$2.5M
NIDDK NIH HHS R01 DK113597NIDDK NIH HHS UC4 DK116255
6 · The paper itself

Abstract

Genetically fusing protein domains to Cas9 has yielded several transformative technologies; however, the genetic modifications are limited to natural polypeptide chains at the Cas9 termini, which excludes a diverse array of molecules useful for gene editing. Here, we report chemical modifications that allow site-specific and multiple-site conjugation of a wide assortment of molecules on both the termini and internal sites of Cas9, creating a platform for endowing Cas9 with diverse functions. Using this platform, Cas9 can be modified to more precisely incorporate exogenously supplied single-stranded oligonucleotide donor (ssODN) at the DNA break site. We demonstrate that the multiple-site conjugation of ssODN to Cas9 significantly increases the efficiency of precision genome editing, and such a platform is compatible with ssODNs of diverse lengths. By leveraging the conjugation platform, we successfully engineer INS-1E, a β-cell line, to repurpose the insulin secretion machinery, which enables the glucose-dependent secretion of protective immunomodulatory factor interleukin-10.

Indexed as

Cell EngineeringCell LineCRISPR-Associated Protein 9Gene EditingHumansInsulin Infusion SystemsSynthetic BiologyCRISPR-Associated Protein 9

Identifiers

PMID32792475
PMCPMC7426819

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.