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Barcoded DNA structures for the subcellular profiling of proteins

Barcoded DNA nanostructures for the multiplexed profiling of subcellular protein distribution

This issue highlights tumour-cell-derived microparticles as efficient drug-delivery carriers, the boosting of chemotherapy in colonic tumours via the phage-guided modulation of gut microbiota, the delivery of a therapeutic monoclonal antibody to metastases in the central nervous system, the augmentation of canonical Wnt signalling to produce cell factories of therapeutically potent exosomes, integrated glass microelectrodes for in vivo brain electrophysiology, and barcoded DNA nanostructures for the profiling of subcellular protein distribution.

The cover illustrates tetrahedral DNA nanostructures that act as barcodes for the high-throughput multiplexed profiling of the subcellular expression and distribution of proteins in cells.

Massively parallel DNA sequencing is established, yet high-throughput protein profiling remains challenging. Here, we report a barcoding approach that leverages the combinatorial sequence content and the configurational programmability of DNA nanostructures for high-throughput multiplexed profiling of the subcellular expression and distribution of proteins in whole cells. The barcodes are formed by in situ hybridization of tetrahedral DNA nanostructures and short DNA sequences conjugated with protein-targeting antibodies, and by nanostructure-assisted ligation (either enzymatic or chemical) of the nanostructures and exogenous DNA sequences bound to nanoparticles of different sizes (which cause these localization sequences to differentially distribute across subcellular compartments). Compared with linear DNA barcoding, the nanostructured barcodes enhance the signal by more than 100-fold. By implementing the barcoding approach on a microfluidic device for the analysis of rare patient samples, we show that molecular subtypes of breast cancer can be accurately classified and that subcellular spatial markers of disease aggressiveness can be identified.

By Sundah et al.

Nature Biomedical Engineering volume 3pages684–694 (2019)

 

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