Evidence map›Paper›PMID 23287859›Full record

ArticleBlood2013

TLR9-mediated siRNA delivery for targeting of normal and malignant human hematopoietic cells in vivo.

Qifang Zhang, Dewan Md Sakib Hossain, Sergey Nechaev, Anna Kozlowska, Wang Zhang, Yong Liu, Claudia M Kowolik, Piotr Swiderski, John J Rossi, Stephen Forman and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

57 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
  2. Cell-selective telomere damage by thiopurine-based oligonucleotide for diffuse large B cell lymphoma immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  3. Review
  4. Local CpG-Molecular therapy. Nucleic acids · 2024
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Targeted In Vivo Delivery of NF-κB Decoy Inhibitor Augments Sensitivity of B Cell Lymphoma to Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. 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

15 authors at 4 institutions in 3 countries.

Qifang ZhangDepartment of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute at City of Hope, Duarte, CA 91010, USA.
Dewan Md Sakib Hossain
Sergey Nechaev
Anna Kozlowska
Wang Zhang
Yong Liu
Claudia M Kowolik
Piotr Swiderski
John J Rossi
Stephen Forman
Sumanta Pal
Ravi Bhatia
Andrew Raubitschek
Hua Yu
Marcin Kortylewski
Beckman Research InstituteInstitute of Molecular Medicine · INCity of Hope · USPoznan University of Medical Sciences · PL

Funding

Transplant for Lymphoma:Therapy-Related LeukemiaP50CA107399 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI FORMAN, STEPHEN J, KWAK, LARRY W · 2004 to 2022
$35.5M
Role of Stat3 in Tumor Immune Evasion and Immune SuppressionR01CA122976 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI YU, HUA E · 2006 to 2015
$2.9M
CpG-siRNA Conjugates to Target Acute Myeloid LeukemiaR01CA155367 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI KORTYLEWSKI, MARCIN · 2011 to 2015
$1.7M
Targeting Stat3 to Improve ImmunotherapyR01CA140692 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI YU, HUA E · 2009 to 2013
$1.7M
NCI NIH HHS P50 CA107399NCI NIH HHS R01 CA122976NCI NIH HHS R01 CA140692NCI NIH HHS R01CA146092NCI NIH HHS R01 CA155367NCI NIH HHS R01CA155367
6 · The paper itself

Abstract

STAT3 operates in both cancer cells and tumor-associated immune cells to promote cancer progression. As a transcription factor, it is a highly desirable but difficult target for pharmacologic inhibition. We have recently shown that the TLR9 agonists CpG oligonucleotides can be used for targeted siRNA delivery to mouse immune cells. In the present study, we demonstrate that a similar strategy allows for targeted gene silencing in both normal and malignant human TLR9(+) hematopoietic cells in vivo. We have developed new human cell-specific CpG(A)-STAT3 siRNA conjugates capable of inducing TLR9-dependent gene silencing and activation of primary immune cells such as myeloid dendritic cells, plasmacytoid dendritic cells, and B cells in vitro. TLR9 is also expressed by several human hematologic malignancies, including B-cell lymphoma, multiple myeloma, and acute myeloid leukemia. We further demonstrate that oncogenic proteins such as STAT3 or BCL-X(L) are effectively knocked down by specific CpG(A)-siRNAs in TLR9(+) hematologic tumor cells in vivo. Targeting survival signaling using CpG(A)-siRNAs inhibits the growth of several xenotransplanted multiple myeloma and acute myeloid leukemia tumors. CpG(A)-STAT3 siRNA is immunostimulatory and nontoxic for normal human leukocytes in vitro. The results of the present study show the potential of using tumoricidal/immunostimulatory CpG-siRNA oligonucleotides as a novel 2-pronged therapeutic strategy for hematologic malignancies.

Indexed as

AnimalsCell Line, TumorGenetic TherapyGene Transfer TechniquesHematologic NeoplasmsHematopoietic Stem CellsHumansLeukemia, Myeloid, AcuteLymphomaMiceMice, Inbred BALB CMice, Inbred NODMice, KnockoutMice, SCIDMultiple MyelomaNeoplasm TransplantationCPG-oligonucleotideOligodeoxyribonucleotidesRNA, Small InterferingSTAT3 protein, humanSTAT3 Transcription FactorTLR9 protein, humanToll-Like Receptor 9

Identifiers

PMID23287859
PMCPMC3578952
OpenAlexW2014723748

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.