Evidence map›Paper›PMID 37550425›Full record

ArticleNature biomedical engineering2024

Computational optimization of antibody humanness and stability by systematic energy-based ranking.

Ariel Tennenhouse, Lev Khmelnitsky, Razi Khalaila, Noa Yeshaya, Ashish Noronha, Moshit Lindzen, Emily K Makowski, Ira Zaretsky, Yael Fridmann Sirkis, Yael Galon-Wolfenson and 5 more

Abstract read
In one paragraph

Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. A SynB1-conjugated antibody cocktail crosses the blood-brain barrier to produce a therapeutic effect on rabies.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Designing stable humanized antibodies.Nature biomedical engineering · 2024
    Article
  20. 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

15 authors.

Ariel TennenhouseDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Lev KhmelnitskyDepartment of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.ORCID http://orcid.org/0000-0002-0719-8027
Razi KhalailaDepartment of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
Noa YeshayaDepartment of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.ORCID http://orcid.org/0000-0003-0385-870X
Ashish NoronhaDepartment of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
Moshit LindzenDepartment of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
Emily K MakowskiBiointerfaces Institute and Departments of Chemical Engineering, Pharmaceutical Sciences and Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Ira ZaretskyAntibody Engineering Unit, Weizmann Institute of Science, Rehovot, Israel.
Yael Fridmann SirkisProtein Analysis Unit, Weizmann Institute of Science, Rehovot, Israel.
Yael Galon-WolfensonProtein Analysis Unit, Weizmann Institute of Science, Rehovot, Israel.
Peter M TessierBiointerfaces Institute and Departments of Chemical Engineering, Pharmaceutical Sciences and Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3220-007X
Jakub AbramsonDepartment of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
Yosef YardenDepartment of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
Deborah FassDepartment of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Sarel J FleishmanDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel. sarel@weizmann.ac.il.ORCID http://orcid.org/0000-0003-3177-7560

Funding

Design and Evolution of Polyvalent Domain Antibodies Specific for Tau AggregatesRF1AG059723 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KANE, RAVI S., TESSIER, PETER M · 2018 to 2022
$2.4M
Structure-guided antibody targeting of pre-selected epitopes in amyloidogenic aggregatesR35GM136300 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESSIER, PETER M · 2020 to 2024
$1.5M
NIA NIH HHS RF1 AG059723NIGMS NIH HHS R35 GM136300
6 · The paper itself

Abstract

Conventional methods for humanizing animal-derived antibodies involve grafting their complementarity-determining regions onto homologous human framework regions. However, this process can substantially lower antibody stability and antigen-binding affinity, and requires iterative mutational fine-tuning to recover the original antibody properties. Here we report a computational method for the systematic grafting of animal complementarity-determining regions onto thousands of human frameworks. The method, which we named CUMAb (for computational human antibody design; available at http://CUMAb.weizmann.ac.il ), starts from an experimental or model antibody structure and uses Rosetta atomistic simulations to select designs by energy and structural integrity. CUMAb-designed humanized versions of five antibodies exhibited similar affinities to those of the parental animal antibodies, with some designs showing marked improvement in stability. We also show that (1) non-homologous frameworks are often preferred to highest-homology frameworks, and (2) several CUMAb designs that differ by dozens of mutations and that use different human frameworks are functionally equivalent.

Indexed as

AntibodiesComplementarity Determining RegionsAnimalsHumansAntibodiesComplementarity Determining Regions

Identifiers

PMID37550425
PMCPMC10842793

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.