| I think ∼3E−5 per base per replication. Might be a more useful number [1]. If you use 10mers, that only gives you 1048576. I'd be almost certain that >90% of those sequences also exist in the human genome. So your target isn't specific enough (take out stuff you need as the parent suggested). So you need to use a longer sequence, perhaps 25bp. Maybe there's a stable region or set of regions you can target (in which case the high overall mutation rate doesn't matter). Or a cocktail of sequences, specific to the global HIV population (I doubt this, HIV mutates more in a single individual than Flu does in the global population). But if not, then you first need to figure out what the viral population in this individual looks like. So you sequence a subset of population, and come up with a 25mer or set of 25mers that target this population. That might be a lot of sequences (significant problem). Which you then need to get synthesized (will take weeks). Now. It's taken days to run your sequencing experiment, and weeks to get your CRISPR stuff synthesized. In this time the viral population has been generating 10E11 new virions per day. You're population has moved on, and almost certainly contains members which don't have your previous cocktail of 25mers in them and will survive the treatment. Because HIV mutates so much, there was some interesting work I saw a while back on guiding the evolution of the population. You'd use drugs which don't wipe out the infection, but push the population toward specific genotypes. Specifically those which you have good treatments for, in the hope that you can wipe out most of the population at once. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530041/ |
Hmm... I would bet that there is a cocktail of sequences such that if they are not conserved, the virus effectively becomes no longer HIV (no longer infectious, no longer capable of producing symptoms...).
HIV is obviously not a human being, right? Find every sequence where it differs, target them all. :-)