CRISPR-Cas12a (Cpf1) proteins are RNA-guided enzymes that bind and cut DNA as 
components of bacterial adaptive immune systems. Like CRISPR-Cas9, Cas12a has 
been harnessed for genome editing on the basis of its ability to generate 
targeted, double-stranded DNA breaks. Here we show that RNA-guided DNA binding 
unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a 
that completely degrades ssDNA molecules. We find that target-activated, 
nonspecific single-stranded deoxyribonuclease (ssDNase) cleavage is also a 
property of other type V CRISPR-Cas12 enzymes. By combining Cas12a ssDNase 
activation with isothermal amplification, we create a method termed DNA 
endonuclease-targeted CRISPR trans reporter (DETECTR), which achieves attomolar 
sensitivity for DNA detection. DETECTR enables rapid and specific detection of 
human papillomavirus in patient samples, thereby providing a simple platform for 
molecular diagnostics.