The development of an Electrochemical Biosensor for Cas12 -Mediated DNA Hairpins

Osteopetrosis (OPT) is a genetic disease characterized by abnormally increased bone density due to unbalanced bone formation and bone resorption. Autosomal Dominant Osteopetrosis type 2(ADOII) caused by Chloride Channel 7 gene (CLCN7) mutant, has highest morbidity. While Whole Exome Sequencing (WES) can effectively detect and diagnose mutant genotype, early diagnosis remains a challenge. To solve these unmet need, our work proposed a electrochemical single mutation biosensor, developed with targeting Cas12a cleaving interfacial hpDNA. The practical application ability of adjustable hpDNA sequence and portable detection devices were demonstrated in the proposal as well [8-11]. We proposed an in-vivo Au@Gd biosensor, further modified with SIQV amino acid chain to target osteoclasts and reduce systematic side effect in drug delivery. Gold (Au) nanoparticle is able to provide a stronger signal in CT images and non-equilibrium electron spins in (Gd)(III) will produce strong magnetic moments. AuNP coupling Gd(III) complex achieve multi-modal imaging with accurate correspondences. In summary, our research help inform strategies outweighs traditional gene detection biosensor with novel SNP detection method. And our biosensor significantly outperforms the original multi-modal imaging with targeting and therapeutic effect. We hope that our research will encourage more researchers to focus on clinical unmet need and built up the bridge between bench side and bed side.