Evidence map›Paper›PMID 35217666›Full record

ArticleNature communications2022

Investigation of Cas9 antibodies in the human eye.

Marcus A Toral, Carsten T Charlesworth, Benjamin Ng, Teja Chemudupati, Shota Homma, Hiromitsu Nakauchi, Alexander G Bassuk, Matthew H Porteus, Vinit B Mahajan

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. 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 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Peeling back the layers of immunogenicity in Cas9-based genomic medicine.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  5. Article
  6. CRISPR/Cas9 Delivery Systems to Enhance Gene Editing Efficiency.International journal of molecular sciences · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023
    Review
  11. Genome editing in the treatment of ocular diseases.Experimental & molecular medicine · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Precision genome editing in the eye.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  18. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 2 countries.

Marcus A ToralMolecular Surgery Program, Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USA.
Carsten T CharlesworthDepartment of Pediatrics, Stanford University, Palo Alto, CA, USA.
Benjamin NgMolecular Surgery Program, Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-4296-2948
Teja ChemudupatiMolecular Surgery Program, Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USA.
Shota HommaDepartment of Genetics, Stanford University, Palo Alto, CA, USA.
Hiromitsu NakauchiDepartment of Genetics, Stanford University, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-9841-6973
Alexander G BassukDepartments of Pediatrics and Neurology and The Iowa Neuroscience Institute (INI), University of Iowa, Iowa City, IA, USA.ORCID http://orcid.org/0000-0002-4067-2157
Matthew H PorteusDepartment of Pediatrics, Stanford University, Palo Alto, CA, USA. mporteus@stanford.edu.ORCID http://orcid.org/0000-0002-3850-4648
Vinit B MahajanMolecular Surgery Program, Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USA. vinit.mahajan@stanford.edu.ORCID http://orcid.org/0000-0003-1886-1741
Palo Alto University · USStanford University · USUniversity of Iowa · USCalifornia Institute for Regenerative Medicine · USUniversity of Oxford · GBVA Palo Alto Health Care System · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007337 · NIGMS · UNIVERSITY OF IOWA · PI GEYER, PAMELA K., LENTZ, STEVEN R · 1985 to 2020
$15.9M
Stanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI Jeffrey L Goldberg · 2017 to 2026
$8.0M
Medical Scientist Training ProgramT32GM139776 · NIGMS · UNIVERSITY OF IOWA · PI Gordon F Buchanan · 2021 to 2026
$6.4M
Gene Silencing and Gene Editing in PhototransductionR01EY024698 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Stephen H Tsang · 2015 to 2026
$4.7M
Inflammatory Gene Transcription in the RetinaR01EY030151 · NEI · STANFORD UNIVERSITY · PI BASSUK, ALEXANDER G, MAHAJAN, VINIT B · 2020 to 2024
$2.0M
Proteomic Biomarkers of Intraocular InfectionR01EY031952 · NEI · STANFORD UNIVERSITY · PI BASSUK, ALEXANDER G, FERGUSON, POLLY J · 2020 to 2023
$1.6M
Mechanism-based therapies for photoreceptor degenerationR01EY025225 · NEI · UNIVERSITY OF IOWA · PI MAHAJAN, VINIT B · 2015 to 2018
$1.3M
NEI NIH HHS P30 EY026877NEI NIH HHS R01 EY024698NEI NIH HHS R01 EY025225NEI NIH HHS R01 EY030151NEI NIH HHS R01 EY031952NIGMS NIH HHS T32 GM007337NIGMS NIH HHS T32 GM139776
6 · The paper itself

Abstract

Preexisting immunity against Cas9 proteins in humans represents a safety risk for CRISPR-Cas9 technologies. However, it is unclear to what extent preexisting Cas9 immunity is relevant to the eye as it is targeted for early in vivo CRISPR-Cas9 clinical trials. While the eye lacks T-cells, it contains antibodies, cytokines, and resident immune cells. Although precise mechanisms are unclear, intraocular inflammation remains a major cause of vision loss. Here, we used immunoglobulin isotyping and ELISA platforms to profile antibodies in serum and vitreous fluid biopsies from human adult subjects and Cas9-immunized mice. We observed high prevalence of preexisting Cas9-reactive antibodies in serum but not in the eye. However, we detected intraocular antibodies reactive to S. pyogenes-derived Cas9 after S. pyogenes intraocular infection. Our data suggest that serum antibody concentration may determine whether specific intraocular antibodies develop, but preexisting immunity to Cas9 may represent a lower risk in human eyes than systemically.

Indexed as

CRISPR-Associated Protein 9CRISPR-Cas SystemsAnimalsAntibodiesHumansMiceStreptococcus pyogenesT-LymphocytesAntibodiesCRISPR-Associated Protein 9

Identifiers

PMID35217666
PMCPMC8881612
OpenAlexW4214628568

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.