Evidence map›Paper›PMID 19033646›Full record

ArticleThe Journal of clinical investigation2009

Harnessing endogenous miR-181a to segregate transgenic antigen receptor expression in developing versus post-thymic T cells in murine hematopoietic chimeras.

Eirini P Papapetrou, Damian Kovalovsky, Laurent Beloeil, Derek Sant'angelo, Michel Sadelain

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.9field-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

36 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. miRNA-mediated control of exogenousMolecular therapy. Methods & clinical development · 2022
    Article
  5. Review
  6. Identification of Acute Myeloid Leukemia Bone Marrow Circulating MicroRNAs.International journal of molecular sciences · 2020
    Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. MicroRNA-regulated viral vectors for gene therapy.World journal of experimental medicine · 2016
    Review
  13. Article
  14. Review
  15. Article
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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

5 authors at 1 institution in 1 country.

Eirini P PapapetrouCenter for Cell Engineering, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
Damian Kovalovsky
Laurent Beloeil
Derek Sant'angelo
Michel Sadelain
Memorial Sloan Kettering Cancer Center · US

Funding

TUMORICIDAL FUNCTIONS OF T LYMPHOCYTES IN PSMA TUMORSP01CA059350 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI O'REILLY, RICHARD JOHN · 1992 to 2012
$21.4M
GLOBIN GENE TRANSFER FOR THERAPY OF SICKLE CELL ANEMIAR01HL057612 · NHLBI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SADELAIN, MICHEL · 1996 to 2004
$1.5M
NCI NIH HHS CA59350NCI NIH HHS P01 CA059350NHLBI NIH HHS R01 HL057612NHLBI NIH HHS R01 HL57612
6 · The paper itself

Abstract

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression by targeting complementary sequences, referred to as miRNA recognition elements (MREs), typically located in the 3' untranslated region of mRNAs. miR-181a is highly expressed in developing thymocytes and markedly downregulated in post-thymic T cells. We investigated whether endogenous miR-181a can be harnessed to segregate expression of chimeric antigen receptors (CARs) and TCRs between developing and mature T cells. Lentiviral-encoded antigen receptors were tagged with a miR-181a-specific MRE and transduced into mouse BM cells that were used to generate hematopoietic chimeras. Expression of a CAR specific for human CD19 (hCD19) was selectively suppressed in late double-negative and double-positive thymocytes, coinciding with the peak in endogenous miR-181a expression. Receptor expression was fully restored in post-thymic resting and activated T cells, affording protection against a subsequent challenge with hCD19+ tumors. Hematopoietic mouse chimeras engrafted with a conalbumin-specific TCR prone to thymic clonal deletion acquired peptide-specific T cell responsiveness only when the vector-encoded TCR transcript was similarly engineered to be subject to regulation by miR-181a. These results demonstrate the potential of miRNA-regulated transgene expression in stem cell-based therapies, including cancer immunotherapy.

Indexed as

AnimalsBone Marrow CellsCell LineageChimeraHematopoietic Stem CellsHumansLymphocyte ActivationMiceMice, TransgenicMicroRNAsReceptors, AntigenReceptors, Antigen, T-CellRecombinant Fusion ProteinsThymus GlandT-LymphocytesTransgenesMicroRNAsmirn181 microRNA, mouseReceptors, AntigenReceptors, Antigen, T-CellRecombinant Fusion Proteins

Identifiers

PMID19033646
PMCPMC2613472
OpenAlexW2019585591

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.