Evidence map›Paper›PMID 26053072›Full record

ArticlePlant biotechnology journal2015

Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice.

Jin Su, Alexandra Sherman, Phillip A Doerfler, Barry J Byrne, Roland W Herzog, Henry Daniell

Open access · bronzeAbstract read
In one paragraph

Article in Plant biotechnology journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

42 citing papers in PubMed, 57 citations in OpenAlex.

  1. Plant-Based Systems for Producing Therapeutic Proteins: Current Status and Future Prospects.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  2. Article
  3. Progress and Challenges in the Treatment of Fabry Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Jin SuDepartment of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alexandra ShermanDepartment of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA.
Phillip A DoerflerDepartment of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA.
Barry J ByrneDepartment of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA.
Roland W HerzogDepartment of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA.
Henry DaniellDepartment of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
University of Florida · USUniversity of Pennsylvania · US

Funding

Using social networks to map and evaluate team science across CTSA hubsUL1TR001427 · NCATS · UNIVERSITY OF FLORIDA · PI MITCHELL, DUANE A. · 2015 to 2024
$37.2M
Oral immune modulatory therapy using antigens bioencapsulated in plant cellsR01HL107904 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DANIELL, HENRY · 2011 to 2023
$7.5M
Training In Rehabilitation and Neuromuscular PlasticityT32HD043730 · NICHD · UNIVERSITY OF FLORIDA · PI DAVID D FULLER · 2003 to 2026
$5.3M
Oral Therapy for Hemophilia AR01HL109442 · NHLBI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, HERZOG, ROLAND W. · 2011 to 2015
$3.5M
Expression of Human Therapeutic Proteins in Transgenic Tobacco ChloroplastsR01GM063879 · NIGMS · UNIVERSITY OF CENTRAL FLORIDA · PI DANIELL, HENRY · 2002 to 2010
$2.0M
NCATS NIH HHS UL1 TR001427NHLBI NIH HHS R01 HL107904NHLBI NIH HHS R01 HL109442NICHD NIH HHS T32 HD043730NIGMS NIH HHS R01 GM063879
6 · The paper itself

Abstract

Deficiency of acid alpha glucosidase (GAA) causes Pompe disease in which the patients systemically accumulate lysosomal glycogen in muscles and nervous systems, often resulting in infant mortality. Although enzyme replacement therapy (ERT) is effective in treating patients with Pompe disease, formation of antibodies against rhGAA complicates treatment. In this report, we investigated induction of tolerance by oral administration of GAA expressed in chloroplasts. Because full-length GAA could not be expressed, N-terminal 410-amino acids of GAA (as determined by T-cell epitope mapping) were fused with the transmucosal carrier CTB. Tobacco transplastomic lines expressing CTB-GAA were generated through site-specific integration of transgenes into the chloroplast genome. Homoplasmic lines were confirmed by Southern blot analysis. Despite low-level expression of CTB-GAA in chloroplasts, yellow or albino phenotype of transplastomic lines was observed due to binding of GAA to a chloroplast protein that has homology to mannose-6 phosphate receptor. Oral administration of the plant-made CTB-GAA fusion protein even at 330-fold lower dose (1.5 μg) significantly suppressed immunoglobulin formation against GAA in Pompe mice injected with 500 μg rhGAA per dose, with several-fold lower titre of GAA-specific IgG1 and IgG2a. Lyophilization increased CTB-GAA concentration by 30-fold (up to 190 μg per g of freeze-dried leaf material), facilitating long-term storage at room temperature and higher dosage in future investigations. This study provides the first evidence that oral delivery of plant cells is effective in reducing antibody responses in ERT for lysosomal storage disorders facilitating further advances in clinical investigations using plant cell culture system or in vitro propagation.

Indexed as

Antibody FormationAdministration, Oralalpha-GlucosidasesAnimalsChloroplastsCholera ToxinDisease Models, AnimalEnzyme Replacement TherapyEpitopesGene ExpressionGenetic VectorsGlycogen Storage Disease Type IIHumansMiceNicotianaPhenotypealpha-GlucosidasesCholera ToxinEpitopesGAA protein, humanRecombinant Fusion Proteinsbioencapsulationenzyme replacement therapylysosomal storage disordermolecular farmingoral tolerancePompe disease

Identifiers

PMID26053072
PMCPMC4578979
OpenAlexW2129472357

What OpenQuestion holds

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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.