ArticleProceedings of the National Academy of Sciences of the United States of America2023
In vivo selection of synthetic nucleocapsids for tissue targeting.
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 7 papers.
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Who cites it
7 citing papers in PubMed.
- In vitro-reconstituted Drosophila Arc capsids deliver gene editors to dystrophic muscle.bioRxiv : the preprint server for biology · 2026Article
- Engineering complexity into protein-based biomaterials for biomedical applications.Nature reviews. Materials · 2026Article
- A Nonviral Neo-Nucleocapsid for Cell-Specific RNA Delivery Developed by Pseudo-Cyclic Peptide Grafting and Directed Evolution.Angewandte Chemie (International ed. in English) · 2026Article
- Local structural flexibility drives oligomorphism in computationally designed protein assemblies.Nature structural & molecular biology · 2025Article
- Nonviral protein cages as tools to decipher and combat viral threats.Npj viruses · 2025Review
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- Organ- and Cell-Selective Delivery of mRNA In Vivo Using Guanidinylated Serinol Charge-Altering Releasable Transporters.Journal of the American Chemical Society · 2024Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Controlling the biodistribution of protein- and nanoparticle-based therapeutic formulations remains challenging. In vivo library selection is an effective method for identifying constructs that exhibit desired distribution behavior; library variants can be selected based on their ability to localize to the tissue or compartment of interest despite complex physiological challenges. Here, we describe further development of an in vivo library selection platform based on self-assembling protein nanoparticles encapsulating their own mRNA genomes (synthetic nucleocapsids or synNCs). We tested two distinct libraries: a low-diversity library composed of synNC surface mutations (45 variants) and a high-diversity library composed of synNCs displaying miniproteins with binder-like properties (6.2 million variants). While we did not identify any variants from the low-diversity surface library that yielded therapeutically relevant changes in biodistribution, the high-diversity miniprotein display library yielded variants that shifted accumulation toward lungs or muscles in just two rounds of in vivo selection. Our approach should contribute to achieving specific tissue homing patterns and identifying targeting ligands for diseases of interest.
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Registered trials
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