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Nanoparticle-Based Discrimination of Single-Nucleotide Polymorphism in Long DNA Sequences.

María Sanromán-IglesiasCharles H LawrieLuis M Liz-MarzánMarek Grzeliczak
Published in: Bioconjugate chemistry (2017)
Circulating DNA (ctDNA) and specifically the detection cancer-associated mutations in liquid biopsies promises to revolutionize cancer detection. The main difficulty however is that the length of typical ctDNA fragments (∼150 bases) can form secondary structures potentially obscuring the mutated fragment from detection. We show that an assay based on gold nanoparticles (65 nm) stabilized with DNA (Au@DNA) can discriminate single nucleotide polymorphism in clinically relevant ssDNA sequences (70-140 bases). The preincubation step was crucial to this process, allowing sequential bridging of Au@DNA, so that single base mutation can be discriminated, down to 100 pM concentration.
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