Lee, K. et al. Nat. Nanotechnol. doi:10.1038/nnano.2014.73 (20 April 2014).

Alternative splicing is an important form of post-transcriptional regulation, and disease states have been linked to incorrectly spliced transcripts. Methods are needed to quantitatively assess splicing in living cells. Lee et al. functionalized gold nanoparticles with either of two oligonucleotides that target opposite sides of a splice junction. Binding of both primers at a splice junction brings the nanoparticles into close proximity, resulting in a spectral shift that can be distinguished by hyperspectral plasmon resonance imaging. The method can detect smaller splicing differences than similar methods that use two fluorophores. The researchers showed that specific splice forms of breast cancer susceptibility gene 1 (BRCA1) can be detected and quantified down to the single-molecule level in vitro and in living cells.