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revised on 11.11.2019 and posted on 20.11.2019by Jiajun Wang, Meng-Yin Li, Jie Yang, Ya-Qian Wang, Xue-Yuan Wu, Jin Huang, Yi-Lun Ying, Yi-Tao Long
DNA lesion such as
metholcytosine(mC), 8-OXO-guanine(OG), inosine(I) etc
could cause the genetic diseases. Identification of the varieties of lesion
bases are usually beyond the capability of conventional DNA sequencing which is
mainly designed to discriminate four bases only. Therefore, lesion detection
remain challenge due to the massive varieties and less distinguishable readouts
for minor structural variations. Moreover, standard amplification and labelling
hardly works in DNA lesions detection. Herein, we designed a single molecule
interface from the mutant K238Q Aerolysin, whose confined sensing region shows
the high compatible to capture and then directly convert each base lesion into
distinguishable current readouts. Compared with previous single molecule
sensing interface, the resolution of the K238Q Aerolysin nanopore is enhanced
by 2-order. The novel K238Q could direct discriminate at least 3 types (mC,
OG, I) lesions without lableing and quantify modification sites
under mixed hetero-composition condition of oligonucleotide. Such nanopore
could be further applied to diagnose genetic diseases at high sensitivity.