Evidence map›Paper›PMID 35263584›Full record

ArticleCell reports2022

Targeted intracellular delivery of Cas13 and Cas9 nucleases using bacterial toxin-based platforms.

Songhai Tian, Yang Liu, Evan Appleton, Huan Wang, George M Church, Min Dong

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

19 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. A Chemically Induced CRISPR/dCas13Journal of medicinal chemistry · 2025
    Article
  6. Review
  7. Targeted degradation of α-Synuclein using an evolved botulinum toxin protease.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
  17. Insights Gained from RNA Editing Targeted by the CRISPR-Cas13 Family.International journal of molecular sciences · 2022
    Review
  18. Review
  19. Review
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

6 authors at 2 institutions in 2 countries.

Songhai TianDepartment of Urology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Microbiology and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA. Electronic address: songhai.tian@childrens.harvard.edu.
Yang LiuDepartment of Urology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Microbiology and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA; Department of Nephrology, The First Hospital of Jilin University, Changchun, 130021, China.
Evan AppletonDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
Huan WangDepartment of Urology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Microbiology and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
George M ChurchDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
Min DongDepartment of Urology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Microbiology and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA. Electronic address: min.dong@childrens.harvard.edu.
Boston Children's Hospital · USHarvard University · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2M
Structure and Function of C. Difficile ToxinsR01AI139087 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Min Dong, Rongsheng Jin · 2018 to 2026
$7.4M
Long-term effects of botulinum neurotoxins on neuronal viabilityR01NS080833 · NINDS · HARVARD MEDICAL SCHOOL · PI Min Dong · 2013 to 2026
$6.8M
Molecular basis of action and pathogenesis of Clostridium difficile toxin BR01AI132387 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI DONG, MIN · 2017 to 2021
$3.5M
Targeted Delivery of Therapeutics into Motor Neurons for Post-exposure Treatment of BotulismR01NS117626 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI DONG, MIN · 2021 to 2025
$3.3M
Molecular mechanism for retrograde transport of tetanus neurotoxinR21NS106159 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI DONG, MIN · 2018 to 2019
$487k
NIAID NIH HHS R01 AI132387NIAID NIH HHS R01 AI139087NICHD NIH HHS P30 HD018655NIDDK NIH HHS P30 DK034854NINDS NIH HHS R01 NS080833NINDS NIH HHS R01 NS117626NINDS NIH HHS R21 NS106159
6 · The paper itself

Abstract

Targeted delivery of therapeutic proteins toward specific cells and across cell membranes remains major challenges. Here, we develop protein-based delivery systems utilizing detoxified single-chain bacterial toxins such as diphtheria toxin (DT) and botulinum neurotoxin (BoNT)-like toxin, BoNT/X, as carriers. The system can deliver large protein cargoes including Cas13a, CasRx, Cas9, and Cre recombinase into cells in a receptor-dependent manner, although delivery of ribonucleoproteins containing guide RNAs is not successful. Delivery of Cas13a and CasRx, together with guide RNA expression, reduces mRNAs encoding GFP, SARS-CoV-2 fragments, and endogenous proteins PPIB, KRAS, and CXCR4 in multiple cell lines. Delivery of Cre recombinase modifies the reporter loci in cells. Delivery of Cas9, together with guide RNA expression, generates mutations at the targeted genomic sites in cell lines and induced pluripotent stem cell (iPSC)-derived human neurons. These findings establish modular delivery systems based on single-chain bacterial toxins for delivery of membrane-impermeable therapeutics into targeted cells.

Indexed as

Bacterial ToxinsCOVID-19CRISPR-Cas SystemsGene EditingHumansRNA, Guide, CRISPR-Cas SystemsSARS-CoV-2Bacterial ToxinsRNA, Guide, CRISPR-Cas Systemsbotulinum neurotoxinCas13Cas9CreCRISPR-Cas9diphtheria toxingenome editingintracellular deliverySARS-CoV-2toxin

Identifiers

PMID35263584
PMCPMC8958846
OpenAlexW4220932765

What OpenQuestion holds

Textmetadata
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.