In vitro and in vivo base editing of CCR5 in hematopoietic stem cells confers HIV-1 resistance - PubMed
2 hours ago
- #CCR5 knockout
- #base editing
- #HIV gene therapy
- Researchers developed an HIV gene therapy strategy using in vivo precision gene editing in hematopoietic stem cells (HSCs).
- Helper-dependent adenoviral vectors expressing all-in-one base editors (HDAd-BEs) were created to target the CCR5 gene.
- In vitro tests showed near-complete CCR5 knockout and significant inhibition of HIV infection in treated cells.
- Human CD34+ cells from mobilized donors or cord blood showed efficient base editing after HDAd-BE transduction.
- T cell differentiation and HIV infection experiments demonstrated lower HIV genome titers with CCR5 base editing.
- In vivo studies in humanized mice showed ~50% CCR5 base editing in bone marrow cells and ~12-fold lower HIV plasma titers.
- No significant off-target effects or adverse reactions were observed.
- This approach offers a potential functional cure for HIV by creating HIV-resistant cells in vivo.