Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells [RNA-Seq Exp1]

Here we present a virus-like particle (VLP)-based toolkit that delivers diverse CRISPR genome editing modalities to human monocytes, macrophages, and dendritic cells with high efficiency while preserving viability and innate immune responsiveness.

VLP-mediated delivery of ribonucleoprotein payloads supports gene knockout, base editing, and epigenetic silencing. Furthermore, in combination with AAV-mediated donor delivery, this approach enables site-specific integration of large DNA sequences via homology-directed repair. We also developed SLICeVLP, a system combining sgRNA delivery via VPX-lentivirus with Cas9 protein delivery via engineered virus-like particles (eVLPs), and applied it to perform pooled loss-of-function screens and Perturb-seq in human macrophages.