HpE12

HpE12 is a therapeutic polypurine reverse Hoogsteen hairpin (PPRH) oligonucleotide designed to lower cholesterol levels by targeting the PCSK9 gene. Developed by researchers at the University of Barcelona and the University of Oregon, HpE12 is a single-stranded DNA molecule that binds specifically to the polypyrimidine sequence of exon 12 of the PCSK9 gene via Watson-Crick and Hoogsteen bonds. This binding inhibits gene transcription and the action of RNA polymerase, effectively silencing PCSK9 expression. The resulting reduction in PCSK9 protein levels prevents the degradation of low-density lipoprotein receptors (LDLR), thereby increasing LDL cholesterol uptake by cells and reducing circulating plasma cholesterol. In preclinical studies using transgenic mice, HpE12 demonstrated significant efficacy, reducing plasma PCSK9 levels by 50% and cholesterol levels by 47% within three days of a single injection, offering a potential statin-free alternative for managing hypercholesterolemia.

Other names

polypurine reverse Hoogsteen hairpin E12PPRH-E12PPRH-E-12PPRH-E 12