Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies
Projected steady-state values for: (a) HIV and TIP production from dually infected cells at the single-cell level; (b) HIV and TIP viral loads at the individual patient level in vivo; and (c) HIV/AIDS prevalence at the population level. At each scale, values are plotted as a function of two molecular-level design criteria: (i) the expression-level of TIP genomic mRNA over HIV genomic mRNA (parameter P from the intracellular model, see Text S1), and (ii) TIP-encoded inhibition of HIV gene expression (parameter D from the intracellular model, see Text S1) where 1.0 corresponds to complete inhibition of HIV, 0.0 corresponds to no inhibition of HIV (when D = 0.0, HIV viral load is reduced only by ‘wasting’ of HIV genomes in nonviable heterozygous virions). TIPs lacking active inhibition of HIV display higher production at the single-cell level and, counter-intuitively, inhibit HIV more potently at the individual patient level and at the population level by outcompeting HIV for targets. Purple ‘HIV escape’ arrows represent the direction of HIV evolution to evade direct inhibition by TIP-encoded molecules.