CD4-directed Nanoblades enable selective genome editing in CD4+ cells and HIV suppression in vitro and in vivo

ABSTRACT: Current antiretroviral therapies suppress HIV replication but fail to eliminate integrated proviral DNA in long-lived CD4⁺ cells, precluding a cure. CRISPR-Cas9 offers potential for HIV eradication but efficient and cell-specific delivery into HIV target cells remains a major hurdle. We developed CD4-directed Nanoblades (CD4-NBs), murine leukemia virus-like particles pseudotyped with anti-CD4 nanobodies and a fusogenic glycoprotein VSV Gmut, to selectively deliver Cas9-gRNA ribonucleoproteins into CD4⁺ cells. CD4-NBs selectively delivered cargo to CD4⁺ cells in vitro and in vivo, achieving efficient gene disruption in primary CD4 cells. Dual-guide CD4-NBs targeting conserved HIV tat/rev/env regions disrupted proviral DNA, suppressing HIV infection in CD4 cells. In HIV-infected, ART-pretrea

SUBMITTER: Jolien Van Cleemput 

PROVIDER: S-SCDT-10_1038-S44321-026-00481-X | biostudies-other |

REPOSITORIES: biostudies-other