PNA-RENTAC

PNA-RENTAC is a renal-targeted RNA therapeutic platform consisting of peptide nucleic acids (PNAs) conjugated to a Renal Tubule-targeting Carbohydrate (RENTAC) ligand. The RENTAC ligand, composed of acetylated lactobionic acid on a lysine/hexanediamine scaffold, facilitates selective delivery to the proximal convoluted tubules (PCTs) of the kidney via megalin/cubilin-mediated endocytosis. This conjugation strategy is designed to overcome the glomerular barrier and rapid urinary clearance typically associated with oligonucleotide therapies. In preclinical models, PNA-RENTAC conjugates targeting miR-33 (PNA33-RENTAC) have demonstrated significant renal miR-33 knockdown, leading to the upregulation of fatty acid oxidation genes and a reduction in fibrotic markers and collagen deposition. The platform is being developed for the treatment of kidney diseases, including kidney fibrosis.