Histidine-Lysine Polymer

Histidine-Lysine Polymer (HKP) is a synthetic, branched polypeptide delivery platform designed for the transport and intracellular release of nucleic acid therapeutics, including siRNA, mRNA, and tRNA fragments. Developed by Dr. A. James Mixson and utilized primarily by **Sirnaomics**, HKP consists of a lysine backbone with multiple branches containing histidine and lysine residues. The lysine components facilitate the formation of nanoparticles through electrostatic interactions with negatively charged nucleic acids, while the histidine residues provide a "proton sponge" effect that promotes endosomal escape by buffering the acidic environment of the endosome, ensuring the cargo reaches the cytoplasm. HKP is the core delivery technology for several clinical-stage candidates, most notably **STP705** (a dual siRNA targeting TGF-β1 and COX-2) for the treatment of various cancers and fibrotic conditions. In recent respiratory research (e.g., PMID 41875736), HKP has been employed to deliver Ginkgo biloba-derived tRNA fragments to the lungs to treat asthma by restoring mitochondrial homeostasis and targeting the PMEPA1 gene.

Other names

HK polymerHistidine-Lysine branched peptide