In theory, a helicase can be attacked by (i) inhibition of NTPase activity through direct competition for NTP binding, (ii) inhibition of substrate binding through direct competition at active site, (iii) allosteric mechanisms to affect NTPbinding/NTP hydrolysis and/or polynucleotide binding, and (iv) inhibition of unwinding activity by steric hinderance of helicase translocation along the polynucleotide substrate (83, 84) . Because the NTP-binding and substrate-binding pockets may be sufficiently similar between various helicases, specificity of inhibition through these sites will likely be extremely difficult, although perhaps not impossible. On the other hand, the tremendous variations in sequence and sizes of helicases, in their oligomerization states, in their discrete domains responsible for protein-protein interactions and/or for targeting to specific nucleic acids (85) , and in their differential localizations within cells (86) offer interventional possibilities outside of the NTP-or polynucleotidebinding sites.