Evidence map›Paper›PMID 40808259›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Precision T cell correction platform for inborn errors of immunity.

Katariina Mamia, Solrun Kolbeinsdottir, Kornel Labun, Zhuokun Li, Anna Komisarczuk, Salla Keskitalo, Ganna Reint, Frida Loe Haugen, Britt Olaug Lindestad, Siv Skundberg Jensen and 22 more

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Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

32 authors.

Katariina MamiaCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Department of Pediatrics, Oslo University Hospital, 0372 Oslo, Norway; Precision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway.
Solrun KolbeinsdottirDepartment of Oncology-Pathology, Karolinska Institutet, 17177 Stockholm, Sweden.
Kornel LabunComputational Biology Unit, Department of Informatics, University of Bergen, 5008 Bergen, Norway.
Zhuokun LiCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway.
Anna KomisarczukCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Precision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway.
Salla KeskitaloSystems Biology/Pathology Research Group, University of Helsinki, 00014 Helsinki, Finland; Institute of Biotechnology, HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
Ganna ReintCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway.
Frida Loe HaugenCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Precision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway.
Britt Olaug LindestadCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Precision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway.
Siv Skundberg JensenCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Precision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway.
Thea Johanne GjerdingenPrecision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
Antti TuhkalaInstitute of Biotechnology, HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
Carolina Wieczorek ErvikCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Precision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway.
Pavel KopcilCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Precision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway.
Nail FatkhutdinovCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway.
Karen Helene Bronken MartinsenDivision of Pediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway.
Hans Christian ErichsenDivision of Pediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway.
Monika SzymanskaCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Precision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway.
Eero TölöMinistry of Finance, 0030 Oslo, Norway.
Virpi GlumoffResearch Unit of Internal Medicine and Biomedicine, University of Oulu, 90014 Oulu, Finland; ERN-RITA Core Center Member, RITAFIN Consortium, Infectious Diseases Clinic, Oulu University Hospital, 90220 Oulu, Finland.
Janna SaarelaCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Institute for Molecular Medicine Finland, HiLIFE, 00290 Helsinki, Finland; Department of Medical Genetics, Oslo University Hospital, 0450 Oslo, Norway.
Trond Melbye MichelsenDepartment of Obstetrics, Division of Obstetrics and Gynecology, Oslo University Hospital, 0424 Oslo, Norway.
Camilla Schalin-JänttiEndocrinology, Abdominal Center, Helsinki University Hospital, 00029 Helsinki, Finland; University of Helsinki, ENDO-ERN (European Reference Network on Rare Endocrine Conditions), 00290 Helsinki, Finland.
Johanna OlweusPrecision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
Eira LeinonenFolkhälsan Institute of Genetics, and Stem Cells and Metabolism Research Program, University of Helsinki, 00014 Helsinki, Finland.
Markku VarjosaloSystems Biology/Pathology Research Group, University of Helsinki, 00014 Helsinki, Finland; Institute of Biotechnology, HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
Eivind ValenComputational Biology Unit, Department of Informatics, University of Bergen, 5008 Bergen, Norway; Department of Biosciences, University of Oslo, 0371 Oslo, Norway.
Timo HautalaResearch Unit of Internal Medicine and Biomedicine, University of Oulu, 90014 Oulu, Finland; ERN-RITA Core Center Member, RITAFIN Consortium, Infectious Diseases Clinic, Oulu University Hospital, 90220 Oulu, Finland.
Martin EngeDepartment of Oncology-Pathology, Karolinska Institutet, 17177 Stockholm, Sweden.
Timi MarteliusInflammation Center, Department of Infectious Disease, Helsinki University Hospital and University of Helsinki, 00029 Helsinki, Finland.
Shiva Dahal-KoiralaCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Precision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway.
Emma HaapaniemiCentre for Molecular Medicine Norway, University of Oslo, 0318 Oslo, Norway; Department of Pediatrics, Oslo University Hospital, 0372 Oslo, Norway; Precision Immunotherapy Alliance, University of Oslo, 0379 Oslo, Norway. Electronic address: e.m.haapaniemi@ncmm.uio.no.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CRISPR-Cas9 gene editing is a promising tool to correct pathogenic variants for autologous cell therapies targeting inborn errors of immunity (IEI). Current strategies, such as gene knockout or cDNA knockin, address many single-gene defects but can disrupt gene expression, highlighting the need for precise correction platforms. While transplanting corrected autologous hematopoietic stem cells is a curative approach, it is unsuitable for patients with advanced disease, inflammation, or acute infections. As correcting T cells is an alternative therapeutic strategy for lymphoid IEIs, we present an efficient T cell single-nucleotide variant (SNV) correction platform based on homology-directed repair (HDR). By using STAT1 gain-of-function, cartilage hair hypoplasia, deficiency of ADA2, and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy as IEI models, we demonstrate that our platform achieves up to 80% correction, with resultant functional correction of the disease phenotype in the selected models. Furthermore, we performed safety profiling using GUIDE-seq, single-cell RNA sequencing, long-read genome sequencing, and proteomics analysis and detected no genomic, transcriptomic, or proteomic aberrations. This study establishes HDR-based SNV editing as a portable method for developing clinical autologous T cell therapies and represents a promising step toward a broad-spectrum gene correction platform for treating diverse monogenic immune disorders.

Indexed as

Gene EditingT-LymphocytesAnimalsCRISPR-Cas SystemsDisease Models, AnimalGenetic TherapyHumansMiceSTAT1 Transcription FactorSTAT1 Transcription Factorautologous T cell therapyCRISPR-Cas9 gene correctionex vivo gene editinggene therapyhomology-directed repairinborn errors of immunitynon-viral genome editingplatform technologyprimary T cell editingsingle-nucleotide variant correction

Identifiers

PMID40808259
PMCPMC12628183

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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.