Customizable virus-like particles deliver CRISPR–Cas9 ribonucleoprotein for effective ocular neovascular and Huntington’s disease gene therapy

In vivo CRISPR gene editing holds enormous potential for various diseases. Ideally, CRISPR delivery should be cell type-specific and time-restricted for optimal efficacy and safety, but customizable methods are lacking. Here we develop a cell-tropism programmable CRISPR-Cas9 ribonucleoprotein delivery system (RIDE) based on virus-like particles. The efficiency of RIDE was comparable to that of adeno-associated virus and lentiviral vectors and higher than lipid nanoparticles. RIDE could be readily reprogrammed to target dendritic cells, T cells and neurons, and significantly ameliorated the disease symptoms in both ocular neovascular and Huntington's disease models via cell-specific gene editing. In addition,…

• A
  AstraZeneca
• CF
  CHDI Foundation
• AU
  Aarhus Universitet
• UC
  University College London
• NN
  National Natural Science Foundation of China

  Awards: 31971364, 81970766, 82171102
• SJ
  Shanghai Jiao Tong University

  Award: 21TQ1400204
• FR
  Fundamental Research Funds for the Central Universities

  Award: 24X010201944
• OE
  Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center)