Figure 1.

A theoretical model of TRIM5α gene therapy for HIV cure. This flow diagram demonstrates a theoretical model for ex vivo gene editing in hematopoietic stem cells (HSCs) to effect the R332P substitution using the newly described SaCRISPR-Cas9 system. HSCs harvested from an HIV-positive patient would be transduced with an adeno-associated virus (AAV) vector bearing the Cas9 apparatus, sgRNAs targeting TRIM5, and a repair template. A mixed population of HSCs would then be reinfused and among them, transgenic long-term repopulating HSCs would engraft, resulting in a durable subset of anti-HIV CD4⁺ T cells with a survival advantage in the face of viral challenge.