SCREENING AND USE OF AGENTS WHICH BLOCK OR ACTIVATE INTEIN SPLICING UTILIZING NATURAL OR HOMOLOGOUS EXTEINS

摘要

Positive genetic selection systems are provided with methods for screening agents that control intein-mediated protein splicing innative host proteins - exteins - or in homologous exteins. Agents inhibiting or activating protein splicing are detected by eithercell viability or cell death where a positive genetic selection system uses a cell comprising, as in Figure 9, a first gene encoding a wild type enzyme, or a drug-resistant enzyme, and a second gene encoding a dominant cytotoxic form of the enzyme comprising an intein, or a drug-susceptible cytotoxic form of the enzyme comprising an intein. Non-lethal selection systems and assays are further provided as well as exemplary mycobacterial gyrase- and helicase-associated inteins. Also provided are controllable inteins and methods for in vivo control of drug delivery and methods for in vivo control of protein expression wherein protein splicing is modulated.