Evidence map›Paper›PMID 39187662›Full record

ArticleNature biomedical engineering2025

Robust genome and cell engineering via in vitro and in situ circularized RNAs.

Michael Tong, Nathan Palmer, Amir Dailamy, Aditya Kumar, Hammza Khaliq, Sangwoo Han, Emma Finburgh, Madeleine Wing, Camilla Hong, Yichen Xiang and 8 more

Abstract read
In one paragraph

Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. IVT-free, chemically synthesized protein-encoding RNA oligonucleotides for rapid production of personalized cancer vaccines.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  16. Emerging clinical applications of ADAR based RNA editing.Stem cells translational medicine · 2025
    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

18 authors.

Michael TongDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Nathan PalmerBiological Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA.
Amir DailamyDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Aditya KumarDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Hammza KhaliqDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Sangwoo HanDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Emma FinburghDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Madeleine WingDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
Camilla HongDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Yichen XiangDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Katelyn MiyasakiDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Andrew PortellDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Joseph RainaldiBiomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA.
Amanda SuhardjoDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Sami NourreddineDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Wei Leong ChewGenome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
Ester J KwonDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Prashant MaliDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA. pmali@ucsd.edu.ORCID http://orcid.org/0000-0002-3383-1287

Funding

Bridge2AI: Cell Maps for AI (CM4AI) Data Generation ProjectOT2OD032742 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jean-Christophe Bélisle-Pipon, TIMOTHY W CLARK · 2022 to 2026
$21.5M
TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3M
The Cancer Cell Map Initiative v2.0U54CA274502 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trey Ideker · 2022 to 2026
$14.2M
Next generation massively multiplexed combinatorial genetic screensR01HG012351 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Trey Ideker, Prashant Mali · 2023 to 2026
$2.7M
UC San Diego Genetics Training ProgramT32GM145427 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRUCE A HAMILTON · 2022 to 2026
$2.6M
Nanoscale Biomaterials for Targeted Repair in Traumatic Brain InjuryDP2NS111507 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KWON, ESTER J. · 2018 to 2018
$2.4M
NEURAXIAL AAVS TARGETING DRG CHANNELS INVOLVED IN CHRONIC POST INFLAMMATORY PAINR01NS131560 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TONY L. YAKSH · 2024 to 2026
$1.8M
Training in Bioengineering Research and Technology Development in Cardiovascular in Cardiopulmonary Health and DiseaseT32HL160507 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Karen L Christman, Andrew D. McCulloch · 2022 to 2026
$1.6M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
American Heart Association (American Heart Association, Inc.) AHA 916973NCI NIH HHS U54 CA274502NHGRI NIH HHS R01 HG012351NHLBI NIH HHS T32 HL160507NIGMS NIH HHS P41 GM103504NIGMS NIH HHS T32 GM145427NIH HHS OT2 OD032742NIH HHS S10 OD026929NINDS NIH HHS DP2 NS111507NINDS NIH HHS R01 NS131560U.S. Department of Defense (United States Department of Defense) W81XWH-22-1-0401U.S. Department of Health & Human Services | National Institutes of Health (NIH) DP2NS111507U.S. Department of Health & Human Services | National Institutes of Health (NIH) OT2OD032742U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER) U54CA274502
6 · The paper itself

Abstract

Circularization can improve RNA persistence, yet simple and scalable approaches to achieve this are lacking. Here we report two methods that facilitate the pursuit of circular RNAs (cRNAs): cRNAs developed via in vitro circularization using group II introns, and cRNAs developed via in-cell circularization by the ubiquitously expressed RtcB protein. We also report simple purification protocols that enable high cRNA yields (40-75%) while maintaining low immune responses. These methods and protocols facilitate a broad range of applications in stem cell engineering as well as robust genome and epigenome targeting via zinc finger proteins and CRISPR-Cas9. Notably, cRNAs bearing the encephalomyocarditis internal ribosome entry enabled robust expression and persistence compared with linear capped RNAs in cardiomyocytes and neurons, which highlights the utility of cRNAs in these non-dividing cells. We also describe genome targeting via deimmunized Cas9 delivered as cRNA and a long-range multiplexed protein engineering methodology for the combinatorial screening of deimmunized protein variants that enables compatibility between persistence of expression and immunogenicity in cRNA-delivered proteins. The cRNA toolset will aid research and the development of therapeutics.

Indexed as

Cell EngineeringGenomeRNARNA, CircularAnimalsCRISPR-Cas SystemsGene EditingHEK293 CellsHumansIntronsMiceMyocytes, CardiacNeuronsRNARNA, Circular

Identifiers

PMID39187662
PMCPMC12186994

What Socratic holds

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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 Socratic graph.