Evidence map›Paper›PMID 42331836›Full record

ArticleNature communications2026

Probing the limits of genetic recoding using multi-omics-guided evolution.

Akos Nyerges, Anush Chiappino-Pepe, Bogdan Budnik, Maximilien Baas-Thomas, Elissa Rhuby, Regan Flynn, Shirui Yan, Nili Ostrov, Min Liu, Meizhou Wang and 21 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

31 authors.

Akos NyergesDepartment of Genetics, Harvard Medical School, Boston, MA, USA. akos_nyerges@hms.harvard.edu.ORCID 0000-0002-1581-490X
Anush Chiappino-Pepe *Department of Genetics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3993-907X
Bogdan Budnik *Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.ORCID 0000-0003-3622-2003
Maximilien Baas-ThomasDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-9821-9585
Elissa RhubyDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Regan FlynnDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Shirui YanDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Nili OstrovDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Min LiuGenScript USA Inc., Piscataway, NJ, USA.
Meizhou WangGenScript USA Inc., Piscataway, NJ, USA.
Qingmei ZhengGenScript USA Inc., Piscataway, NJ, USA.
Fangxiang HuGenScript USA Inc., Piscataway, NJ, USA.
Kangming ChenGenScript USA Inc., Piscataway, NJ, USA.
Alexandra RudolphDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Dawn ChenDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8127-6014
Jenny AhnDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID 0009-0000-3912-7162
Owen SpencerDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Venkat AyalavarapuDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Angela TarverDOE Joint Genome Institute (JGI), Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Miranda Harmon-SmithDOE Joint Genome Institute (JGI), Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID 0000-0002-3980-1820
Matthew HamiltonDOE Joint Genome Institute (JGI), Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Ian BlabyDOE Joint Genome Institute (JGI), Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID 0000-0002-1631-3154
Yasuo YoshikuniDOE Joint Genome Institute (JGI), Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID 0000-0002-8372-640X
Behnoush HajianCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Adeline JinGenScript USA Inc., Piscataway, NJ, USA.
Balint KintsesInstitute of Biochemistry, HUN-REN Biological Research Centre, Szeged, Hungary.ORCID 0000-0003-0844-0310
Monika SzamelInstitute of Biochemistry, HUN-REN Biological Research Centre, Szeged, Hungary.
Viktoria SeregiInstitute of Biochemistry, HUN-REN Biological Research Centre, Szeged, Hungary.
Yue ShenBGI Research, Shenzhen, China.ORCID 0000-0002-3276-7295
Zilong LiGenScript USA Inc., Piscataway, NJ, USA.
George M ChurchDepartment of Genetics, Harvard Medical School, Boston, MA, USA. gchurch@genetics.med.harvard.edu.ORCID 0000-0001-6232-9969

Funding

Development of a Gene-Transfer-Resistant and Biocontained Next-Generation Bacterial Host for Controlled Drug DeliveryR00EB035165 · NIBIB · HARVARD MEDICAL SCHOOL · PI Akos Nyerges · 2026 to 2026
$249k
Development of a Gene-Transfer-Resistant and Biocontained Next-Generation Bacterial Host for Controlled Drug DeliveryK99EB035165 · NIBIB · HARVARD MEDICAL SCHOOL · PI NYERGES, AKOS · 2023 to 2024
$237k
DOE | Office of Science (SC) DE-AC02-05CH11231European Molecular Biology Organization (EMBO) LTF 160-2019 Long-Term fellowshipNIBIB NIH HHS K99 EB035165NIBIB NIH HHS R00 EB035165U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) 1K99EB035165-01U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) 4R00EB035165-03U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) 5K99EB035165-02
6 · The paper itself

Abstract

Engineering the genetic code-by reassigning multiple of the 64 natural codons-enables making organisms resistant to all viruses, preventing genetic information exchange, and allowing the biosynthesis of genetically encoded unnatural polymers. However, synonymous codon replacement-recoding-is frequently lethal, and how recoding impacts fitness remains poorly explored. Here, we explore these effects using genome synthesis, directed evolution, and genome-transcriptome-translatome-proteome co-profiling on multiple synthetic Escherichia coli genomes. We construct six partially recoded E. coli strains bearing up to 45.8% of a synthetic genome with a deleterious 57-codon genetic code. As our analyses revealed widespread defects-including unassigned codons in Syn61 and Syn57-we apply multi-omics to revise our genome design and mitigate defects. Using multi-omics, we show that recoding induces transcriptional and translational changes leading to fitness defects under hundreds of conditions. Finally, we develop a multi-omics-guided evolution strategy that rapidly restores fitness, enabling genome synthesis with radical changes.

Indexed as

Directed Molecular EvolutionEscherichia coliGenetic CodeCodonEvolution, MolecularGenetic FitnessGenome, BacterialMultiomicsProtein BiosynthesisTranscriptomeCodon

Identifiers

PMID42331836
PMCPMC13287592

What OpenQuestion holds

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Registered trials

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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.