Predictors of Hepatitis B Cure Using Gene Therapy to Deliver DNA Cleavage Enzymes: A Mathematical Modeling Approach
Figure 2
Intracellular HBV DNA cleavage enzyme pharmacodynamics.
(a) An HBV infected cell with three cccDNA molecules (green circles), and delivery of DNA cleavage enzyme containing vectors (red viruses) can transition to several states where none, some, or all of the episomes are eliminated and/or become resistant to the cleavage enzyme. Arrow thickness denotes the relative probability of each event. (b) Cleavage enzymes (red wavy lines) may bind HBV cccDNA molecules cooperatively, whereby binding of one enzyme to its target sequence enhances binding of other enzymes to the same target on separate episomes. (c) Cleavage enzymes (multi-colored wavy lines) that target separate regions within episomes (thick colored lines of corresponding color) may bind HBV cccDNA molecules cooperatively, whereby binding of one enzyme to its target sequence enhances binding of other enzymes to separate sequences on the same episome.