The article introduces a new CRISPR-based nucleic acid detection method called HOLMES (One-Hour Low-cost Multipurpose highly Efficient System). HOLMES leverages the trans-cleavage activity of Cas12a, a component of the CRISPR-Cas12a system, to detect both DNA and RNA targets. Unlike SHERLOCK, which requires in vitro transcription of DNA to RNA for RNA detection, HOLMES can directly detect DNA targets. The authors tested various Cas12a proteins and found that Lachnospiraceae bacterium ND2006 Cas12a (LbCas12a) performed best. HOLMES demonstrated high sensitivity, with a detectable concentration of 0.1 nM for Cas12a-crRNA and 10 aM when combined with PCR. The method also showed high specificity, capable of discriminating single-base differences in target sequences. HOLMES was successfully applied to human SNP genotyping, detecting DNA viruses like pseudorabies virus (PRV) and RNA viruses like Japanese encephalitis virus (JEV). The authors conclude that HOLMES is a rapid, simple, and efficient method for nucleic acid detection, suitable for medical, environmental, and food monitoring applications.The article introduces a new CRISPR-based nucleic acid detection method called HOLMES (One-Hour Low-cost Multipurpose highly Efficient System). HOLMES leverages the trans-cleavage activity of Cas12a, a component of the CRISPR-Cas12a system, to detect both DNA and RNA targets. Unlike SHERLOCK, which requires in vitro transcription of DNA to RNA for RNA detection, HOLMES can directly detect DNA targets. The authors tested various Cas12a proteins and found that Lachnospiraceae bacterium ND2006 Cas12a (LbCas12a) performed best. HOLMES demonstrated high sensitivity, with a detectable concentration of 0.1 nM for Cas12a-crRNA and 10 aM when combined with PCR. The method also showed high specificity, capable of discriminating single-base differences in target sequences. HOLMES was successfully applied to human SNP genotyping, detecting DNA viruses like pseudorabies virus (PRV) and RNA viruses like Japanese encephalitis virus (JEV). The authors conclude that HOLMES is a rapid, simple, and efficient method for nucleic acid detection, suitable for medical, environmental, and food monitoring applications.