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HIV presents one of the highest evolutionary rates ever detected and combination antiretroviral therapy is needed to overcome the plasticity of the virus population and control viral replication. Conventional treatments lack the ability to clear the latent reservoir, which remains the major obstacle towards a cure. Novel strategies, such as CRISPR/Cas9 gRNA-based genome-editing, can permanently disrupt the HIV genome. However, HIV genome-editing may accelerate viral escape, questioning the feasibility of the approach. Here, we demonstrate that CRISPR/Cas9 targeting of single HIV loci, only partially inhibits HIV replication and facilitates rapid viral escape at the target site. A combinatorial approach of two strong gRNAs targeting different regions of the HIV genome can completely abrogate viral replication and prevent viral escape. Our data shows that the accelerating effect of gene-editing on viral escape can be overcome and as such gene-editing may provide a future alternative for control of HIV-infection.

There were differences in bony morphology between men and women and between subjects with and without ACL injury. The bony morphology that was different between ACL-injured and non-injured subjects varied between male and female subjects.

The results of this study show that there is a significant, but weak correlation between the notch width and the ACL insertion site size. Women had a smaller notch and a smaller insertion site than men. This knowledge could influence pre-operative decision-making with regard to graft choice, single- or double-bundle surgery, and graft size.