LFPRLR SMO

LFPRLR SMO is an experimental splice‑modulating oligomer therapy consisting of a 25‑mer deoxyribonucleic acid morpholino oligomer linked to an octaguanidine dendrimer that selectively blocks inclusion of exon 10 in prolactin receptor (PRLR) pre‑mRNA, thereby preventing synthesis of the long and intermediate isoforms of the prolactin receptor (LF/IFPRLR) while sparing short PRLR isoforms.[1][2][4] By inhibiting signaling of prolactin through the proliferative, anti‑apoptotic long and intermediate PRLR isoforms, LFPRLR SMO downregulates STAT3 activation and decreases expression of oncogenic and survival factors such as MYC and BCL2, leading to reduced survival of malignant B cells and impairment of autoimmune and lymphoproliferative B‑cell expansion in preclinical models.[1][2] In mouse models, systemic administration of LFPRLR SMO reduces pathogenic B‑cell subsets, activation‑induced cytidine deaminase (AID) expression, and the risk of B‑cell malignancy initiation in SLE‑prone and DLBCL‑prone mice, as well as inhibiting growth and progression of overt human diffuse large B‑cell lymphoma xenografts and decreasing breast cancer metastasis while improving survival and enhancing anti‑tumor immune responses.[1][2][3] LFPRLR SMO is being explored as a non‑immunogenic, isoform‑specific strategy targeting PRL–PRLR signaling for the treatment of autoimmune disease and malignant B‑cell and breast cancers, but it remains at a preclinical research stage.[1][2][3][4]

Other names

LF/IFPRLR SMOlong form prolactin receptor splice-modulating oligomerLFPRLR splice-modulating oligomer