ArticleNature biotechnology2017
Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction.
Article in Nature biotechnology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Designing Novel Aspartic Protease (NAP) Using Ancestral Sequence Reconstruction (ASR) for Cheesemaking.Molecular biotechnology · 2026Article
- A resurrected ancestor of Cas12a expands target access and substrate recognition for nucleic acid editing and detection.Nature biotechnology · 2025Article
- The deLIVERed promises of gene therapy: Past, present, and future of liver-directed gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Thermodynamic versus kinetic basis for the high conformational stability of nanobodies for therapeutic applications.FEBS letters · 2025Article
- Artificial Intelligence-Based Approaches for AAV Vector Engineering.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Design of ancestral mammalian alkaline phosphatase bearing high stability and productivity.Applied and environmental microbiology · 2024Article
- Review
- SUPREM: an engineered non-site-specific m6A RNA methyltransferase with highly improved efficiency.Nucleic acids research · 2024Article
- Sequence-encoded bioactive protein-multiblock polymer conjugates via quantitative one-pot iterative living polymerization.Nature communications · 2024Article
- Extant Sequence Reconstruction: The Accuracy of Ancestral Sequence Reconstructions Evaluated by Extant Sequence Cross-Validation.Journal of molecular evolution · 2024Article
- Identification of the Efficient Enhancer Elements in FVIII-Padua for Gene Therapy Study of Hemophilia A.International journal of molecular sciences · 2024Article
- Humanization and functional characterization of enhanced coagulation factor IX variants identified through ancestral sequence reconstruction.Journal of thrombosis and haemostasis : JTH · 2024Article
- Design, structure and plasma binding of ancestral β-CoV scaffold antigens.Nature communications · 2023Article
- ARPIP: Ancestral Sequence Reconstruction with Insertions and Deletions under the Poisson Indel Process.Systematic biology · 2023Article
- Topiary: Pruning the manual labor from ancestral sequence reconstruction.Protein science : a publication of the Protein Society · 2023Article
- Protein Stability: Enhancement and Measurement.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Evolution of CRISPR-associated endonucleases as inferred from resurrected proteins.Nature microbiology · 2023Article
- Enzymatic Conjugation of Modified RNA Fragments by Ancestral RNA Ligase AncT4_2.Applied and environmental microbiology · 2022Article
- Engineering functional thermostable proteins using ancestral sequence reconstruction.The Journal of biological chemistry · 2022Review
- Bypassing evolutionary dead ends and switching the rate-limiting step of a human immunotherapeutic enzyme.Nature catalysis · 2022Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Optimization of a protein's pharmaceutical properties is usually carried out by rational design and/or directed evolution. Here we test an alternative approach based on ancestral sequence reconstruction. Using available genomic sequence data on coagulation factor VIII and predictive models of molecular evolution, we engineer protein variants with improved activity, stability, and biosynthesis potential and reduced inhibition by anti-drug antibodies. In principle, this approach can be applied to any protein drug based on a conserved gene sequence.
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Registered trials
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