ArticleGene therapy2023
Endotoxin contamination in commercially available Cas9 proteins potentially induces T-cell mediated responses.
Article in Gene therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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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.
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.
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Who cites it
5 citing papers in PubMed, 3 citations in OpenAlex.
- Pre-existing antibody and T cell responses to SaCas9, AsCas12a and CasΦ are comparable in naïve individuals.Nature communications · 2026Article
- Recombinant Protein Drugs: A 2025 Update.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Mutations of six amino acid residues in a B domain-deleted blood coagulation factor VIII have a cumulative effect on increasing its secretion.Research and practice in thrombosis and haemostasis · 2026Article
- Immunogenicity of CRISPR therapeutics-Critical considerations for clinical translation.Frontiers in bioengineering and biotechnology · 2023Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Immune responses to Cas proteins have been demonstrated recently and these may prove to be an impediment to their clinical use in gene editing. To make meaningful assessments of Cas9 immunogenicity during drug development and licensure it is imperative the reagents are free of impurities that could affect in vitro assessments of immunogenicity. Here we address the issue of endotoxin levels in laboratory grade Cas9 proteins used to measure T-cell memory responses. Many of these reagents have not been developed for immunogenicity assays, are or microbial origin and carry varying levels of endotoxin. The use of these reagents, off the shelf, without measuring endotoxin levels is likely to introduce incorrect estimates of the prevalence of memory T-cell responses in research studies. We demonstrate wide variation in endotoxin levels in Cas9 proteins from seven suppliers. Different lots from the same supplier also contained varying levels of endotoxin. ELISPOT assays showed similar large variations in the interferon-γ signals. Finally, when we carried out endotoxin depletion in four Cas9 proteins with strong signals in the ELISPOT assay, we found dampening of the interferon-γ signals.
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What OpenQuestion holds
Registered trials
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.