Effect of an α-ammonium boronic acid lipid on transfection activity of a 1,2-diol-containing oxime ether transfection lipid

Authors: Naome Khan, Faisal Ibrahim

SUNY Campus: SUNY Old Westbury

Presentation Type: Poster

Location: Old Union Hall

Presentation #: 27

Timeslot: Session D 3:00-4:00 PM

Abstract: Here, we present an α-ammonium boronic acid (DMDBH) containing cationic lipids for improved silencing activity of transfection lipids. The addition of DMDBH to an LNP-based siRNA formulation comprised of a 1,2-diol-containing transfection lipid, a PEG-containing lipid, a phospholipid (DOPE), and anti-eGFP siRNA improves the silencing activity of the formulation. Three different transfection lipid formulations made from three 1,2-diol-containing lipids were studied and, in each case, the addition of the α-ammonium boronic acid lipid improved overall activity. DMDBH improved the activity of both cationic (OEL4) and ionizable (iOEL4, eiOEL4) transfection lipids. The resultant boronic acid–diol interactions within the liposome bilayers of the lipoplex result in boronate ester formations that covalently link the boronic acid and diol lipids together and strengthen the assembly. The added stability translates to greater intracellular delivery of the RNA payload. Our novel boronic acid lipid is unique and structurally designed to have a low pKa to facilitate favorable equilibrium with diols and form stable hydroxyboronate esters.