Evidence map›Paper›PMID 39367605›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Engineering memory T cells as a platform for long-term enzyme replacement therapy in lysosomal storage disorders.

Evan W Kleinboehl, Kanut Laoharawee, Jacob D Jensen, Joseph J Peterson, Nicholas J Slipek, Bryce J Wick, Matthew J Johnson, Beau R Webber, Branden S Moriarity

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Advances in Therapies for Mucopolysaccharidoses.Current issues in molecular biology · 2026
    Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Evan W KleinboehlDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Kanut LaoharaweeDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Jacob D JensenDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Joseph J PetersonDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Nicholas J SlipekDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Bryce J WickDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Matthew J JohnsonDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Beau R WebberDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: webb0178@umn.edu.
Branden S MoriarityDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: mori0164@umn.edu.

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI SCOTT H KAUFMANN · 2009 to 2026
$37.0M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UM1TR004405 · NCATS · UNIVERSITY OF MINNESOTA · PI Bruce R Blazar, Damien A Fair · 2023 to 2026
$30.8M
Project 4:Targeting M2-like Macrophages and MDSC with Myelolytic-VirotherapyU54CA232561 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI CAIRO, MITCHELL S., CRIPE, TIMOTHY P · 2019 to 2023
$12.1M
Project 3P01CA254849 · NCI · UNIVERSITY OF MINNESOTA · PI LARGAESPADA, DAVID ANDREW, MASOPUST, DAVID · 2021 to 2025
$9.4M
TECH CoreU54CA268069 · NCI · UNIVERSITY OF MINNESOTA · PI David J. Odde · 2022 to 2026
$8.2M
SCGE Disease Models Studies Supplement: Evaluation of prime editing for the amelioration of alpha-1-antitrypsin deficiency in murine and porcine models.U24OD026641 · OD · RECOMBINETICS, INC. · PI CARLSON, DANIEL FRED · 2018 to 2022
$4.1M
Activated NK CAR Cells to Cure HIVR01AI161017 · NIAID · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S, SKINNER, PAMELA J · 2021 to 2025
$3.8M
Deconvoluting the Ewing sarcoma genetic program using ancestry-informed human iPSC modelingR37CA276345 · NCI · UNIVERSITY OF MINNESOTA · PI Beau Richard Webber · 2023 to 2026
$2.2M
Engineered B Cells as a Universal Platform for the Treatment of EnzymopathiesR01AI146009 · NIAID · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S · 2020 to 2024
$1.9M
CTSA Predoctoral T32 at University of MinnesotaT32TR004385 · NCATS · UNIVERSITY OF MINNESOTA · PI Jayne Allyn Fulkerson · 2024 to 2026
$1.3M
CTSA Postdoctoral T32 at University of MinnesotaT32TR004376 · NCATS · UNIVERSITY OF MINNESOTA · PI Jayne Allyn Fulkerson · 2024 to 2026
$1.1M
NCATS NIH HHS T32 TR004376NCATS NIH HHS T32 TR004385NCATS NIH HHS UM1 TR004405NCI NIH HHS P01 CA254849NCI NIH HHS P30 CA077598NCI NIH HHS P50 CA136393NCI NIH HHS R21 CA237789NCI NIH HHS R37 CA276345NCI NIH HHS U54 CA232561NCI NIH HHS U54 CA268069NIAID NIH HHS R01 AI146009NIAID NIH HHS R01 AI161017NIAID NIH HHS R03 AI144840NIAID NIH HHS R21 AI163731NIH HHS U24 OD026641
6 · The paper itself

Abstract

Enzymopathy disorders are the result of missing or defective enzymes. Among these enzymopathies, mucopolysaccharidosis type I is a rare genetic lysosomal storage disorder caused by mutations in the gene encoding alpha-L-iduronidase (IDUA), which ultimately causes toxic buildup of glycosaminoglycans (GAGs). There is currently no cure and standard treatments provide insufficient relief to the skeletal structure and central nervous system (CNS). Human memory T (Tm) cells migrate throughout the body's tissues and can persist for years, making them an attractive approach for cellular-based, systemic enzyme replacement therapy. Here, we tested genetically engineered, IDUA-expressing Tm cells as a cellular therapy in an immunodeficient mouse model of MPS I. Our results demonstrate that a single dose of engineered Tm cells leads to detectable IDUA enzyme levels in the blood for up to 22 weeks and reduced urinary GAG excretion. Furthermore, engineered Tm cells take up residence in nearly all tested tissues, producing IDUA and leading to metabolic correction of GAG levels in the heart, lung, liver, spleen, kidney, bone marrow, and the CNS, although only minimal improved cognition was observed. Our study indicates that genetically engineered Tm cells hold great promise as a platform for cellular-based enzyme replacement therapy for the treatment of mucopolysaccharidosis type I and potentially many other enzymopathies and protein deficiencies.

Indexed as

Disease Models, AnimalEnzyme Replacement TherapyGlycosaminoglycansIduronidaseMucopolysaccharidosis IT-LymphocytesAnimalsHumansImmunologic MemoryLysosomal Storage DiseasesMiceGlycosaminoglycansIduronidaseCRISPR-Cas9gene therapygenome engineeringhomology-directed repairHurler syndromelysosomal storage disordersmemory T cellsmucopolysaccharidosis type I

Identifiers

PMID39367605
PMCPMC11573576

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Registered trials

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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.