Evidence map›Paper›PMID 30127387›Full record

ArticleNature chemical biology2018

Continuous directed evolution of proteins with improved soluble expression.

Tina Wang, Ahmed H Badran, Tony P Huang, David R Liu

Abstract read
In one paragraph

Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing 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

48 citing papers in PubMed.

  1. Article
  2. "Excluded phenotypes" restrict genetic paths toward adaptation in declining populations.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Dosa: A method to covalently barcode proteins for high-throughput biochemistry.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Targeted Transition Mutations in Phage-Assisted Evolution.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Virus-assisted directed evolution of biomolecules.Current opinion in chemical biology · 2023
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. In vivo hypermutation and continuous evolution.Nature reviews. Methods primers · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Tina WangMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Ahmed H BadranMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Tony P HuangMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA. drliu@fas.harvard.edu.

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Continuous Evolution of Proteins with Novel Therapeutic PotentialR01EB022376 · NIBIB · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2019
$1.8M
Engineering Protein Stability Through Phage-Assisted Continuous EvolutionF32GM119228 · NIGMS · HARVARD UNIVERSITY · PI WANG, TINA · 2016 to 2018
$174k
Howard Hughes Medical InstituteNHGRI NIH HHS RM1 HG009490NIBIB NIH HHS R01 EB022376NIGMS NIH HHS F32 GM119228NIGMS NIH HHS R35 GM118062
6 · The paper itself

Abstract

We report the development of soluble expression phage-assisted continuous evolution (SE-PACE), a system for rapidly evolving proteins with increased soluble expression. Through use of a PACE-compatible AND gate that uses a split-intein pIII, SE-PACE enables two simultaneous positive selections to evolve proteins with improved expression while maintaining their desired activities. In as little as three days, SE-PACE evolved several antibody fragments with >5-fold improvement in expression yield while retaining binding activity. We also developed an activity-independent form of SE-PACE to correct folding-defective variants of maltose-binding protein (MBP) and to evolve variants of the eukaryotic cytidine deaminase APOBEC1 with improved expression properties. These evolved APOBEC1 variants were found to improve the expression and apparent activity of Cas9-derived base editors when used in place of the wild-type cytidine deaminase. Together, these results suggest that SE-PACE can be applied to a wide variety of proteins to rapidly improve their soluble expression.

Indexed as

BacteriophagesDirected Molecular EvolutionAPOBEC-1 DeaminaseCytidine DeaminaseEscherichia coliGenomicsHEK293 CellsHumansImmunoglobulin FragmentsInteinsMaltose-Binding ProteinsPromoter Regions, GeneticProtein FoldingProtein SplicingRifampinAPOBEC-1 DeaminaseCytidine DeaminaseImmunoglobulin FragmentsMaltose-Binding ProteinsRifampin

Identifiers

PMID30127387
PMCPMC6143403

What OpenQuestion holds

Textmetadata
LicenceTDM
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.