Site-specific recombinase (SSR)

Site-specific recombinases (SSRs) are a diverse group of enzymes that mediate DNA rearrangements by recognizing and binding to specific short DNA sequences (Grindley et al., 2006). These enzymes catalyze the cleavage and rejoining of DNA strands, facilitating processes such as integration, excision, and inversion of genetic segments without requiring high homology or external energy sources (Brown et al., 2011). They are fundamentally classified into two families, tyrosine and serine recombinases, based on the amino acid residue used for the nucleophilic attack on DNA (Grindley et al., 2006). In clinical medicine, the most prominent members are viral integrases, such as HIV-1 integrase, which are essential for the viral life cycle by incorporating viral DNA into the host genome (Pommier et al., 2005). Consequently, these enzymes are major therapeutic targets for antiviral drugs known as integrase strand transfer inhibitors (INSTIs), including Raltegravir and Dolutegravir (NIH, 2023). Beyond infectious diseases, SSRs like Cre and Flp are utilized as powerful tools in genome engineering and gene therapy to achieve precise genetic modifications (Brown et al., 2011). Their ability to target specific loci makes them ideal for correcting genetic mutations or inserting therapeutic genes into safe harbor sites in the human genome. However, therapeutic use is often limited by challenges such as potential off-target DNA cleavage and the immunogenicity of non-human derived enzymes (Grindley et al., 2006).

Other names

Site-specific integraseDNA recombinaseTyrosine recombinaseSerine recombinaseGenetic recombinaseDNA strand transferase

Inhibition of the strand transfer step of DNA integration, preventing the covalent insertion of viral DNA into the host cell genome (Pommier et al., 2005).