Evidence map›Paper›PMID 31140323›Full record

ArticleHuman gene therapy methods2019

TLR9-Activating CpG-B ODN but Not TLR7 Agonists Triggers Antibody Formation to Factor IX in Muscle Gene Transfer.

John S S Butterfield, Moanaro Biswas, Jamie L Shirley, Sandeep R P Kumar, Alexandra Sherman, Cox Terhorst, Chen Ling, Roland W Herzog

Open access · greenAbstract read
In one paragraph

Article in Human gene therapy methods, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

24 citing papers in PubMed, 28 citations in OpenAlex.

  1. Trial
  2. Article
  3. Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  4. The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
  10. Review
  11. Article
  12. Article
  13. Delivering AAV to the Central Nervous and Sensory Systems.Trends in pharmacological sciences · 2021
    Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Immune Response Mechanisms against AAV Vectors in Animal Models.Molecular therapy. Methods & clinical development · 2020
    Review
  20. A Molecular Revolution in the Treatment of Hemophilia.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Review
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

8 authors at 4 institutions in 2 countries.

John S S Butterfield1 Department of Pediatrics, University of Florida, Gainesville, Florida.
Moanaro Biswas1 Department of Pediatrics, University of Florida, Gainesville, Florida.
Jamie L Shirley1 Department of Pediatrics, University of Florida, Gainesville, Florida.
Sandeep R P Kumar2 Department of Pediatrics, Indiana University, Indianapolis, Indiana.
Alexandra Sherman2 Department of Pediatrics, Indiana University, Indianapolis, Indiana.
Cox Terhorst4 Division of Immunology, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts.
Chen Ling1 Department of Pediatrics, University of Florida, Gainesville, Florida.
Roland W Herzog1 Department of Pediatrics, University of Florida, Gainesville, Florida.
University of Florida · USIndiana University – Purdue University Indianapolis · USBeth Israel Deaconess Medical Center · USFudan University · CN

Funding

Enhancing immune regulation in gene therapy for hemophiliaR01HL131093 · NHLBI · UNIVERSITY OF FLORIDA · PI Ype Peter De Jong, Roland W. Herzog · 2016 to 2026
$7.2M
Immunology of Factor IX Gene Transfer to LiverR01AI051390 · NIAID · UNIVERSITY OF FLORIDA · PI HERZOG, ROLAND W. · 2002 to 2022
$6.7M
Mechanism of high-efficiency transduction of hepatocytes by optimized AAV vectorsR01GM119186 · NIGMS · UNIVERSITY OF FLORIDA · PI ASLANIDI, GEORGE V, SRIVASTAVA, ARUN · 2017 to 2021
$1.5M
NHLBI NIH HHS R01 HL131093NIAID NIH HHS R01 AI051390NIGMS NIH HHS R01 GM119186
6 · The paper itself

Abstract

Innate immune signals that promote B cell responses in gene transfer are generally ill-defined. In this study, we evaluate the effect of activating endosomal Toll-like receptors 7, 8, and 9 (TLR7, TLR7/8, and TLR9) on antibody formation during muscle-directed gene therapy with adeno-associated virus (AAV) vectors. We examined whether activation of endosomal TLRs, by adenine analog CL264 (TLR7 agonist), imidazolquinolone compound R848 (TLR7/8 agonist), or class B CpG oligodeoxynucleotides ODN1826 (TLR9 agonist), could augment antibody formation upon intramuscular administration of AAV1 expressing human clotting factor IX (AAV1-hFIX) in mice. The TLR9 agonist robustly enhanced antibody formation by the 1st week, thus initially eliminating systemic hFIX expression. By contrast, the TLR7 and TLR7/8 agonists did not markedly promote antibody formation, or significantly reduce circulating hFIX. We concurrently investigated the effects of these TLR agonists during muscle gene transfer on mature B cells and dendritic cells (DCs) in the draining lymph nodes including conventional DCs (CD11b

Indexed as

Antibody FormationAdenineAnimalsB-LymphocytesDendritic CellsDependovirusFactor IXGenetic TherapyImidazolesMaleMembrane GlycoproteinsMice, Inbred C57BLOligodeoxyribonucleotidesParvovirinaeQuadriceps MuscleToll-Like Receptor 7AdenineCPG-oligonucleotideFactor IXImidazolesMembrane GlycoproteinsOligodeoxyribonucleotidesresiquimodTlr7 protein, mouseTlr9 protein, mouseToll-Like Receptor 7Toll-Like Receptor 9adeno-associated virusantibodyfactor IXmuscleToll-like receptor

Identifiers

PMID31140323
PMCPMC6590725
OpenAlexW2947646009

What OpenQuestion holds

Textmetadata
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.