Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies

Metzger, Vincent T.; Lloyd-Smith, James O.; Weinberger, Leor S.

Detailed experimental and theoretical study is required to predict the ultimate direction of TIP evolution, but the competing selection pressures may effectively constrain TIP phenotypes to a range that assures low HIV viral load and low HIV disease prevalence. TIP evolution is likely to be dominated by mutational processes, since recombination between TIPs and wild-type HIV appears to be severely limited by fundamental sequence-homology constraints on retroviral recombination [44] that render recombination between full-length 9.7 kb HIV genomes and shorter lentiviral genomes (e.g. TIP) non-competent for integration [18] . This molecular argument against recombination between HIV and TIP is also supported by data from murine models [45, 46] and the recent human clinical trial data [17] , neither of which detected recombination between wild-type HIV-1 and shorter lentiviral therapy vectors.