Gold Nanoparticles Coupled with Synthetic DNA Tails Pinpoint Disease Causing Gene Splice Variants

mRNA splicing is an essential mechanism of gene regulation, but mistakes in the process can cause a number of different diseases. Yet, there aren’t any tools readily available that can provide information about the splice variants that exist inside living cells that are markers for cancer and other conditions. Researchers at Purdue University are now using gold nanoparticles with synthetic DNA tails to detect and measure specific mRNA sequences in live cells.

A single gold nanoparticle, or monomer, appears green when illuminated (top left), while a pair of gold nanoparticles bound to an mRNA splice variant, or dimer, appears reddish (top right). Monomers and dimers also scatter light differently, as shown in the graph above. (Purdue University image / Joseph Irudayaraj)

In an article published in Nature Nanotechnology, the team describes how they used the new complexes to grab onto BRCA1 messenger RNA splice variants that are indicative of breast cancer. Because the gold nanoparticles scatter light differently depending on whether they have a splice variant attached to them, measuring the wavelength of the returning light signal indicates whether the targeted splice variants are present.

From the study abstract:

The probes are made from gold nanoparticles functionalized with oligonucleotides and can hybridize to specific mRNA sequences, forming nanoparticle dimers that exhibit distinct spectral shifts due to plasmonic coupling. With this approach, we show that the spatial and temporal distribution of three selected splice variants of the breast cancer susceptibility gene, BRCA1, can be monitored at single-copy resolution by measuring the hybridization dynamics of the nanoplasmonic dimers. Our study provides insights into RNA and its transport in living cells, which could improve our understanding of cellular protein complexes, pharmacogenomics, genetic diagnosis and gene therapies.

Study in Nature Nanotechnology: Quantitative imaging of single mRNA splice variants in living cells…

Press release: Gold nanoparticles help target, quantify breast cancer gene segments in a living cell…