Duplex-Specific Nuclease (DSN) is an enzyme purified from Kamchatka crab hepatopancreas. DSN displays a strong preference for cleaving double-stranded DNA and DNA in DNA-RNA hybrid duplexes, compared to single-stranded DNA. Moreover, the cleavage rate of short, perfectly matched DNA duplexes by this enzyme is essentially higher than that for non-perfectly matched duplexes of the same length. DSN can be used for cDNA normalization using the novel method developed by Evrogen (Zhulidov et al., Nucl. Acids. Res. 2004, 32: e37), and for other purposes where the high-specific deliverance from the dsDNA is essential.