The escalating growth in computing power and the advent of quantum computing present a critical threat to the security of modern cryptography. Two-factor authentication strategies can effectively resist brute-force attacks to improve the security of access control. Herein, we proposed a two-factor and two-authentication entity strategy based on the trans-cleavage activity of CRISPR-Cas and the "dual-step" sequence-specific cleavage of Pyrococcus furiosus Argonaute. In this strategy, the output of authentication entity 1 acted as a component to operate authentication entity 2, thus enabling a role-based molecular model that implemented access control for the three roles. To further enhance information security, we designed knowledge suppression factors to constitute the command library and possession suppression factors to resist brute-force attacks. This study will promote the development of advanced molecular access control and its applications in biomedical diagnostics and data security.
Keywords: CRISPR-Cas; Pyrococcus furiosus Argonaute; biomolecule-driven authentication; role-based molecular access control; two-factor and two-authentication entity.