Exploring the Trans-Cleavage Activity of CRISPR-Cas12a (cpf1) for the Development of a Universal Electrochemical Biosensor

Yifan Dai, Rodrigo A. Somoza, Liu Wang, Jean F. Welter, Yan Li, Arnold I. Caplan, Chung Chiun Liu

Research output: Contribution to journalReview articlepeer-review

392 Scopus citations

Abstract

An accurate, rapid, and cost-effective biosensor for the quantification of disease biomarkers is vital for the development of early-diagnostic point-of-care systems. The recent discovery of the trans-cleavage property of CRISPR type V effectors makes CRISPR a potential high-accuracy bio-recognition tool. Herein, a CRISPR-Cas12a (cpf1) based electrochemical biosensor (E-CRISPR) is reported, which is more cost-effective and portable than optical-transduction-based biosensors. Through optimizing the in vitro trans-cleavage activity of Cas12a, E-CRIPSR was used to detect viral nucleic acids, including human papillomavirus 16 (HPV-16) and parvovirus B19 (PB-19), with a picomolar sensitivity. An aptamer-based E-CRISPR cascade was further designed for the detection of transforming growth factor β1 (TGF-β1) protein in clinical samples. As demonstrated, E-CRISPR could enable the development of portable, accurate, and cost-effective point-of-care diagnostic systems.

Original languageEnglish
Pages (from-to)17399-17405
Number of pages7
JournalAngewandte Chemie - International Edition
Volume58
Issue number48
DOIs
StatePublished - 25 Nov 2019

Keywords

  • CRISPR Cas12a (cpf1)
  • bioanalytical chemistry
  • biosensor
  • electrochemistry
  • trans-acting cleavage

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