Wang, Juexiao SherryYan, Yan HelenZhang, David Yu2019-12-112019-12-112017Wang, Juexiao Sherry, Yan, Yan Helen and Zhang, David Yu. "Modular probes for enriching and detecting complex nucleic acid sequences." <i>Nature Chemistry,</i> 9, (2017) Springer Nature: 1222-1228. https://doi.org/10.1038/nchem.2820.https://hdl.handle.net/1911/107857Complex DNA sequences are difficult to detect and profile, but are important contributors to human health and disease. Existing hybridization probes lack the capability to selectively bind and enrich hypervariable, long or repetitive sequences. Here, we present a generalized strategy for constructing modular hybridization probes (M-Probes) that overcomes these challenges. We demonstrate that M-Probes can tolerate sequence variations of up to 7 nt at prescribed positions while maintaining single nucleotide sensitivity at other positions. M-Probes are also shown to be capable of sequence-selectively binding a continuous DNA sequence of more than 500 nt. Furthermore, we show that M-Probes can detect genes with triplet repeats exceeding a programmed threshold. As a demonstration of this technology, we have developed a hybrid capture method to determine the exact triplet repeat expansion number in the Huntington's gene of genomic DNA using quantitative PCR.engThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer Nature.Journal articlenihms932420https://doi.org/10.1038/nchem.2820