Evidence map›Paper›PMID 32956624›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021

CRISPR-Cas9-Edited Tacrolimus-Resistant Antiviral T Cells for Advanced Adoptive Immunotherapy in Transplant Recipients.

Leila Amini, Dimitrios Laurin Wagner, Uta Rössler, Ghazaleh Zarrinrad, Livia Felicitas Wagner, Tino Vollmer, Désirée Jacqueline Wendering, Uwe Kornak, Hans-Dieter Volk, Petra Reinke and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. 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
3.8field-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

33 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Effects of CRISPR-Cas9-mediatedMolecular therapy. Methods & clinical development · 2025
    Article
  7. Managing allorejection in off-the-shelf CAR-engineered cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  8. Gene editing of CD3 epsilon to redirect regulatory T cells for adoptive T cell transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  9. Article
  10. Review
  11. Tolerance Induction Strategies in Organ Transplantation: Current Status and Future Perspectives.Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Review
  12. Review
  13. Review
  14. Immunosuppressant therapy averts rejection of allogeneic FKBP1A-disrupted CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  15. Engineering a solution for allogeneic CAR-T rejection.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  16. Article
  17. Review
  18. Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Article
  19. Review of two immunosuppressants: tacrolimus and cyclosporine.Journal of the Korean Association of Oral and Maxillofacial Surgeons · 2023
    Review
  20. Article
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

11 authors at 2 institutions in 1 country.

Leila AminiBerlin Institute of Health (BIH) Center for Regenerative Therapies (B-CRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Dimitrios Laurin WagnerBerlin Institute of Health (BIH) Center for Regenerative Therapies (B-CRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Uta RösslerBerlin Institute of Health (BIH) Center for Regenerative Therapies (B-CRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Institute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Ghazaleh ZarrinradBerlin Institute of Health (BIH) Center for Regenerative Therapies (B-CRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Einstein Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Livia Felicitas WagnerInstitute of Medical Immunology, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Tino VollmerBerlin Institute of Health (BIH) Center for Regenerative Therapies (B-CRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Désirée Jacqueline WenderingBerlin Institute of Health (BIH) Center for Regenerative Therapies (B-CRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Uwe KornakBerlin Institute of Health (BIH) Center for Regenerative Therapies (B-CRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Institute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Hans-Dieter VolkBerlin Institute of Health (BIH) Center for Regenerative Therapies (B-CRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Petra ReinkeBerlin Institute of Health (BIH) Center for Regenerative Therapies (B-CRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Michael Schmueck-HenneresseBerlin Institute of Health (BIH) Center for Regenerative Therapies (B-CRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany. Electronic address: michael.schmueck-henneresse@charite.de.
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · DECharité - Universitätsmedizin Berlin · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Viral infections, such as with cytomegalovirus (CMV), remain a major risk factor for mortality and morbidity of transplant recipients because of their requirement for lifelong immunosuppression (IS). Antiviral drugs often cause toxicity and sometimes fail to control disease. Thus, regeneration of the antiviral immune response by adoptive antiviral T cell therapy is an attractive alternative. Our recent data, however, show only short-term efficacy in some solid organ recipients, possibly because of malfunction in transferred T cells caused by ongoing IS. We developed a vector-free clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-based good manufacturing practice (GMP)-compliant protocol that efficiently targets and knocks out the gene for the adaptor protein FK506-binding protein 12 (FKBP12), required for the immunosuppressive function of tacrolimus. This was achieved by transient delivery of ribonucleoprotein complexes into CMV-specific T cells by electroporation. We confirmed the tacrolimus resistance of our gene-edited T cell products in vitro and demonstrated performance comparable with non-tacrolimus-treated unmodified T cells. The alternative calcineurin inhibitor cyclosporine A can be administered as a safety switch to shut down tacrolimus-resistant T cell activity in case of adverse effects. Furthermore, we performed safety assessments as a prerequisite for translation to first-in-human applications.

Indexed as

CRISPR-Cas SystemsDrug ResistanceGene EditingImmunotherapy, AdoptiveDisease ResistanceGenetic EngineeringHumansImmunosuppressive AgentsTacrolimusT-LymphocytesTransplant RecipientsImmunosuppressive AgentsTacrolimusadoptive T-cell-therapyCMVCRISPR-Cas9drug-resistanceimmunosuppressionimmunotherapysolid-organ-transplantationvector-free gene-editing

Identifiers

PMID32956624
PMCPMC7791012
OpenAlexW3083913990

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.