Nuclease

Nucleases are a diverse superfamily of enzymes responsible for cleaving the phosphodiester bonds that link nucleotides in DNA and RNA molecules. They are fundamentally classified into exonucleases, which degrade nucleic acids from the ends, and endonucleases, which cleave within the chain. These enzymes play essential roles in nearly all aspects of nucleic acid metabolism, including DNA replication, repair of damaged genetic material, and the processing of various RNA species. In a therapeutic context, nucleases serve as both drugs and drug targets. For example, recombinant Deoxyribonuclease I (Dornase alfa) is used to reduce mucus viscosity in cystic fibrosis by degrading extracellular DNA, while programmable nucleases like Cas9 are the engines behind modern gene-editing therapies. Additionally, inhibitors of specific nucleases such as DNA2 or TREX1 are being developed as oncology and immunology treatments to exploit DNA repair vulnerabilities or modulate the STING-mediated immune response. Despite their high therapeutic value, 'Nuclease' is a broad functional category rather than a single specific protein target, requiring further specification for precise drug development.

Other names

Nucleolytic enzymePolynucleotidaseNucleic acid hydrolaseDeoxyribonuclease (DNase)Ribonuclease (RNase)Phosphodiesterase

Nucleases catalyze the hydrolysis of phosphodiester bonds in nucleic acid backbones. Therapeutic strategies include the administration of recombinant nucleases to clear extracellular DNA (e.g., in cystic fibrosis), the use of programmable nucleases for targeted gene editing (e.g., CRISPR-Cas9), and the inhibition of specific repair nucleases to induce synthetic lethality in cancer cells or modulate the innate immune response.