Technology Description

Inventors at the University of Iowa and the University of Connecticut have developed peptide nucleic acid (PNA) miR-122 inhibitors for the prevention and treatment of endothelial dysfunction. PNAs are synthetic DNA mimics in which the phosphodiester backbone is replaced with an N- (2-aminoethyl) glycine backbone. They are enzymatically stable and have a high binding affinity for target sites. Next generation PNAs that include modification at the gamma (γ)-position of the nucleobase, γPNAs, form pre-organized helical structures which confer stronger binding affinity to target sites. The inventors have made further modifications at the γ position of the PNA inhibitor to increase efficacy and biocompatibility of the miR-122 PNA inhibitor (γP-122-I). When tested in vivo, γP-122-I offers near-complete inhibition of endothelial dysfunction and improved glycemic control in high-fat diet mice. Therefore, γP-122-I is a promising molecule for the prevention and treatment of obesity-induced cardiovascular and endothelial disorders.

UIRF Case No. 2022-050

Stage of Development

The novel PNA molecule γP-122-I has been synthesized and tested in vivo using a high-fat diet mouse model. Validation in additional animal models is ongoing.

• Charge-neutral; improved solubility and biocompatibility
• Reduced off-target accumulation; improved efficacy and long-term safety
• Technology can be used to target other miRNAs