Evidence map›Paper›PMID 39642942›Full record

ArticleACS synthetic biology2024

Stem Loop Mediated Transgene Modulation in Human T Cells.

David Mai, Carly Harro, Aabir Sanyal, Philipp C Rommel, Neil C Sheppard, Carl H June

Abstract read
In one paragraph

Article in ACS synthetic biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

6 authors.

David MaiDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0002-9238-0164
Carly HarroCenter for Cellular Immunotherapies, Perelman School of Medicine, Philadelphia, Pennsylvania 19104, United States.
Aabir SanyalDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Philipp C RommelCenter for Cellular Immunotherapies, Perelman School of Medicine, Philadelphia, Pennsylvania 19104, United States.
Neil C SheppardCenter for Cellular Immunotherapies, Perelman School of Medicine, Philadelphia, Pennsylvania 19104, United States.
Carl H JuneCenter for Cellular Immunotherapies, Perelman School of Medicine, Philadelphia, Pennsylvania 19104, United States.

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ronald G Collman · 1999 to 2026
$78.6M
NCI NIH HHS P30 CA016520NIAID NIH HHS P30 AI045008
6 · The paper itself

Abstract

Controlling gene expression is useful for many applications, but current methods often require external user inputs, such as the addition of a drug. We present an alternative approach using cell-autonomous triggers based on RNA stem loop structures in the 3' untranslated regions (UTRs) of mRNA. These stem loops are targeted by the RNA binding proteins Regnase-1 and Roquin-1, allowing us to program stimulation-induced transgene regulation in primary human T cells. By incorporating engineered stem loops into the 3' UTRs of transgenes, we achieved transgene repression through Regnase-1 and Roquin-1 activity, dynamic upregulation upon stimulation, and orthogonal tunability. To demonstrate the utility of this system, we employed it to modulate payloads in CAR-T cells. Our findings highlight the potential of leveraging endogenous regulatory machinery in T cells for transgene regulation and suggest RNA structure as a valuable layer for regulatory modulation.

Indexed as

3' Untranslated RegionsT-LymphocytesTransgenesGene Expression RegulationHumansRNA-Binding ProteinsRNA, Messenger3' Untranslated RegionsRNA-Binding ProteinsRNA, Messenger

Identifiers

PMID39642942
PMCPMC11669162

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.