Evidence map›Paper›PMID 35851375›Full record

ArticleNature biotechnology2023

Engineering circular RNA for enhanced protein production.

Robert Chen, Sean K Wang, Julia A Belk, Laura Amaya, Zhijian Li, Angel Cardenas, Brian T Abe, Chun-Kan Chen, Paul A Wender, Howard Y Chang

Erratum issuedAbstract read
In one paragraph

Article in Nature biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 303 papers.

0numbers the graph read from it
0cells of the map it votes in
303citing 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

303 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026
    Review
  6. Review
  7. Article
  8. Circular Photocaged mRNA for Light-induced Late-stage Activation of Translation.Angewandte Chemie (International ed. in English) · 2026
    Article
  9. PRNA (New York, N.Y.) · 2026
    Article
  10. Codon-optimizedMolecular therapy. Nucleic acids · 2026
    Article
  11. Cold-adapted RNA polymerase fromProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

243 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Robert Chen *Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8141-9687
Sean K Wang *Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1557-8510
Julia A BelkDepartment of Computer Science, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4724-6158
Laura AmayaCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-8742-9111
Zhijian LiDepartment of Chemistry, Stanford University, Stanford, CA, USA.
Angel CardenasCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Brian T AbeCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Chun-Kan ChenCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Paul A WenderDepartment of Chemistry, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-6319-2829
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA. howchang@stanford.edu.ORCID http://orcid.org/0000-0002-9459-4393

Funding

SYNTHETIC STUDIES RELATED TO CANCER RESEARCH/TREATMENTR01CA031845 · NCI · STANFORD UNIVERSITY · PI PAUL Anthony WENDER · 1985 to 2026
$6.9M
Training Program in Adult and Pediatric RheumatologyT32AR050942 · NIAMS · STANFORD UNIVERSITY · PI LEWIS, DAVID BRAM, ROBINSON, WILLIAM H · 2005 to 2025
$6.6M
LncRNA mechanisms in cancerR35CA209919 · NCI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2016 to 2022
$6.4M
Graduate Training Program in BiotechnologyT32GM008412 · NIGMS · STANFORD UNIVERSITY · PI COCHRAN, JENNIFER R · 1991 to 2020
$5.5M
Synthetic Studies Related to Cancer Research/TreatmentR37CA031845 · NCI · STANFORD UNIVERSITY · PI WENDER, PAUL ANTHONY · 2006 to 2015
$4.5M
Stanford Vision Training ProgramT32EY027816 · NEI · STANFORD UNIVERSITY · PI Jeffrey L Goldberg · 2018 to 2026
$2.0M
Systematic identification of RNA sequences and protein components regulating circular RNA translationR00HG011475 · NHGRI · WASHINGTON UNIVERSITY · PI CHEN, CHUN-KAN · 2023 to 2025
$734k
Howard Hughes Medical InstituteNCI NIH HHS R01 CA031845NCI NIH HHS R35 CA209919NCI NIH HHS R37 CA031845NEI NIH HHS T32 EY027816NHGRI NIH HHS R00 HG011475NIAMS NIH HHS T32 AR050942NIGMS NIH HHS T32 GM008412
6 · The paper itself

Abstract

Circular RNAs (circRNAs) are stable and prevalent RNAs in eukaryotic cells that arise from back-splicing. Synthetic circRNAs and some endogenous circRNAs can encode proteins, raising the promise of circRNA as a platform for gene expression. In this study, we developed a systematic approach for rapid assembly and testing of features that affect protein production from synthetic circRNAs. To maximize circRNA translation, we optimized five elements: vector topology, 5' and 3' untranslated regions, internal ribosome entry sites and synthetic aptamers recruiting translation initiation machinery. Together, these design principles improve circRNA protein yields by several hundred-fold, provide increased translation over messenger RNA in vitro, provide more durable translation in vivo and are generalizable across multiple transgenes.

Indexed as

RNARNA, CircularRNA, MessengerRNA SplicingRNARNA, CircularRNA, Messenger

Identifiers

PMID35851375
PMCPMC9931579

What OpenQuestion holds

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LicenceCC BY
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.