Abstract: Compositions and methods are provided for simple, instrument-free and sensitive methods that enable rapid, point-of-care detection of nucleic acid molecules of interest. This is based on a surprising discovery that the relative efficiencies of amplification and CRISPR-based cleavage and detection can be tuned to favor amplification until sufficient amplified products are generated to enable detection. Example approaches include design of guide RNA and primers to target nonoptimal PAM sequences, or sequence-engineering Cas nucleases to reduce activities informing a ribonucleoprotein with the guide RNA or binding to or cleaving the substrate nucleic acid.