{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327357/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327357"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells [RNA-Seq Exp1]","description":"Primary human myeloid cells are promising candidates for immunotherapy, yet efficient and scalable technologies for genetic engineering and screening in these cells are limited. 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. We uncovered regulators of TNF production and CD80 expression in human macrophages, converging on TNFAIP3 as a central regulator of inflammatory polarization. TNFAIP3 ablation promoted a pro-inflammatory cell state that is resistant to suppressive polarization, and augmented cytotoxicity in engineered HER2 CAR-macrophages. Taken together, this platform enables unbiased functional genomics in primary human myeloid cells, with direct implications for myeloid cell therapy design.","dates":{"publication":"2026/04/08"},"accession":"GSE327357","cross_references":{"GSM":["GSM9654299","GSM9654298","GSM9654301","GSM9654300","GSM9654295","GSM9654297","GSM9654296","GSM9654307","GSM9654306","GSM9654308","GSM9654303","GSM9654302","GSM9654305","GSM9654304"],"GPL":["34281"],"GSE":["327357"],"taxon":["Homo sapiens"]}}