Advancing nanopore technology toward protein identification and sequencing

Proteins drive most cellular functions and are key players in diseases, yet proteomics still lags behind genomics due to the complexity, diversity, and dynamic nature of proteoforms. Nanopore technology – known for real-time, single-molecule DNA sequencing – is a promising contender to revolutionize protein analysis. The method has recently been adapted to proteins, showing strong potential for protein identification. However, true de novo protein sequencing with nanopores remains an open challenge. This review compares current nanopore-based strategies for protein analysis and highlights their technical hurdles towards application. Additionally, engineering strategies are explored aiming to bridge the gap towards single-molecule protein analysis and sequencing.