{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331406"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Tumor-targeted degradation of SIRPα reprograms tumor-associated macrophages and restores antitumor immunity","description":"Therapies targeting the CD47–SIRPα \"don't eat me\" axis are currently hampered by limited tissue penetration and dose-limiting hematotoxicity. Here, we report a tumor-targeted mRNA nanotherapeutic that selectively degrades SIRPα on macrophages to unleash antitumor immunity in colorectal cancer. We formulated mRNA encoding an Fc-fused SIRPα degrader into VEGFR2-targeted lipid nanoparticles (LNPs) to achieve tumor-specific delivery. This system triggers lysosomal degradation of SIRPα, repolarizing tumor-associated macrophages toward a pro-inflammatory, phagocytic state that drives CD8⁺ T cell priming. In contrast to the hematologic toxicity associated with systemic CD47 blockade, this strategy demonstrated superior tumor control in syngeneic and orthotopic CRC models while preserving a normal hematologic profile. Single-cell transcriptomics confirmed the remodeling of the immunosuppressive myeloid landscape. These findings establish targeted SIRPα degradation as a potent, safe alternative to systemic CD47 blockade, offering a versatile platform to reprogram myeloid checkpoints in solid tumors.","dates":{"publication":"2026/05/26"},"accession":"GSE331406","cross_references":{"GSM":["GSM9745503","GSM9745504","GSM9745499","GSM9745500","GSM9745501","GSM9745502","GSM9745497","GSM9745498"],"GPL":["28330"],"GSE":["331406"],"taxon":["Mus musculus"]}}