siFmr1

siFmr1 is a **small interfering RNA (siRNA)** therapeutic designed to silence the Fragile X Mental Retardation 1 (Fmr1) gene, which encodes Fragile X Mental Retardation Protein (FMRP). FMRP is notably upregulated in various malignancies including triple-negative breast cancer (TNBC), pancreatic ductal adenocarcinoma, and colon carcinoma, where it mediates immune evasion through multiple mechanisms. The siRNA is delivered via lipid nanoparticles (LNP@siFmr1) using a microfluidic-based electrospray method to achieve passive targeting and accumulation within tumor tissues. Once delivered, siFmr1 silences FMRP expression in tumor cells, leading to recruitment and activation of CD8+ T cells, downregulation of immunosuppressive factors (PROS and IL33), and enhancement of immunostimulatory macrophages and dendritic cells within the tumor microenvironment. The mechanism reprograms the tumor immune microenvironment from "immune-cold" to "immune-hot," making tumors more susceptible to immunotherapy. Preclinical studies demonstrate that siFmr1 synergizes effectively with PD-1 checkpoint inhibitors, achieving approximately 80% tumor growth suppression in combination therapy. The therapeutic strategy addresses immune checkpoint inhibitor resistance by enhancing T-cell infiltration and reversing T-cell exhaustion.