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Fig. 5 | BMC Biology

Fig. 5

From: Viral diversity is an obligate consideration in CRISPR/Cas9 designs for targeting the HIV reservoir

Fig. 5

Simulated reservoir depletion with anti-HIV CRISPR therapy. a Example simulation based on predicted target site conservation (“potency,” ρ = 0.5) and enzyme efficacy to each target site (ϵ = 0.5). CRISPR therapy is dosed weekly, and the average strain contains 100 infected cells (μs = 100). Thin colored lines represent single strains, Ls(t), and the thick black line represents the total reservoir, L(t) = ∑sLs(t). Strains targeted by CRISPR are cleared rapidly, but untargeted strains remain unaffected and the total reservoir size does not decrease below estimated depletion thresholds for functional cure. The dashed line represents a stringent threshold for latent reservoir reduction where patients are expected to remain suppressed for years without cART [15, 16]. See Additional file 4: Figure S3 for simulations varying all parameters. b If 100% coverage (ρ = 1) of target sites can be achieved (either through multiplexing of targets or due to a target site that is highly conserved), enzyme efficacy becomes relevant, dictating the number of doses to cure. At or better than predicted efficacy ϵ > 0.5, doses range between 1 and 5 doses for a median 1 year remission and 5–10 doses for a potentially lifelong absence of viral rebound based on previously estimated thresholds. However, even for 100% coverage, efficacy at 10% or less per dose requires substantial dosing (> 30) to achieve thresholds

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