In this proposal, we aim to design lipid nanoparticles coated with anti-CD4 nanobodies that encode CRISPR/Cas9 ribonucleoproteins targeting both ends of the HIV genome and the viral coreceptor CCR5. As such, our novel nanomedicine will selectively purge HIV reservoirs in CD4+ cells, while conferring healthy CD4+ cells resistant to HIV reinfection, and off-target effects in non-target cells will remain minimal.