ArticleProceedings of the National Academy of Sciences of the United States of America2023
Improving the secretion of designed protein assemblies through negative design of cryptic transmembrane domains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Review
- Engineering complexity into protein-based biomaterials for biomedical applications.Nature reviews. Materials · 2026Article
- Emerging trends in gene and cell therapy: CRISPR in DNA editing and beyond.Cell reports. Medicine · 2026Review
- De novo design of protein nanoparticles with integrated functional motifs.bioRxiv : the preprint server for biology · 2026Article
- Engineering mammalian protein secretion: Toward the convergence of high-throughput biology and computational methods.Cell systems · 2025Review
- Protein nanocages: A new frontier in mucosal vaccine delivery and immune activation.Human vaccines & immunotherapeutics · 2025Review
- From sequence to scaffold: Computational design of protein nanoparticle vaccines from AlphaFold2-predicted building blocks.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Computationally designed mRNA-launched protein nanoparticle immunogens elicit protective antibody and T cell responses in mice.Science translational medicine · 2025Article
- Computational design of bifaceted protein nanomaterials.Nature materials · 2025Article
- A modular mRNA vaccine platform encoding antigen-presenting capsid virus-like particles enhances the immunogenicity of the malaria antigen Pfs25.Nature nanotechnology · 2025Article
- Local structural flexibility drives oligomorphism in computationally designed protein assemblies.Nature structural & molecular biology · 2025Article
- Flexing protein assemblies.Nature structural & molecular biology · 2025Article
- Article
- Accurate computational design of three-dimensional protein crystals.Nature materials · 2023Article
- CELL-E 2: Translating Proteins to Pictures and Back with a Bidirectional Text-to-Image Transformer.Advances in neural information processing systems · 2023Article
- Prospects for developing an Hepatitis C virus E1E2-based nanoparticle vaccine.Reviews in medical virology · 2023Review
- Fast and versatile sequence-independent protein docking for nanomaterials design using RPXDock.PLoS computational biology · 2023Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
Computationally designed protein nanoparticles have recently emerged as a promising platform for the development of new vaccines and biologics. For many applications, secretion of designed nanoparticles from eukaryotic cells would be advantageous, but in practice, they often secrete poorly. Here we show that designed hydrophobic interfaces that drive nanoparticle assembly are often predicted to form cryptic transmembrane domains, suggesting that interaction with the membrane insertion machinery could limit efficient secretion. We develop a general computational protocol, the Degreaser, to design away cryptic transmembrane domains without sacrificing protein stability. The retroactive application of the Degreaser to previously designed nanoparticle components and nanoparticles considerably improves secretion, and modular integration of the Degreaser into design pipelines results in new nanoparticles that secrete as robustly as naturally occurring protein assemblies. Both the Degreaser protocol and the nanoparticles we describe may be broadly useful in biotechnological applications.
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Registered trials
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 Socratic graph.