Single-Stranded Nucleic Acid Transmembrane Molecular Carriers Based on Positively Charged Helical Foldamers

Abstract

Transmembrane delivery of biologically active nucleic acids is an important process in cells and has inspired one to develop advanced drug delivery techniques. In this contribution, molecular-level single-stranded nucleic acid transmembrane carriers are reported based on 3.2 nm long Huc's foldamers (A^OrnQ³Q³)₈ and (^mQ³Q²)₈ with linearly and helically aligned positive charges, respectively. These two foldamers not only show very strong DNA affinity via electrostatic interactions but also discriminatively bind single-stranded DNA (ss-DNA) and double-stranded DNA (ds-DNA), corroborating the importance of precise charge arrangement in the electrostatic interactions. More importantly, these two foldamers are capable of efficiently transporting ss-DNA across the lipid membranes, and the ss-DNA transport activity of (A^OrnQ³Q³)₈ with linearly aligned charges is higher than that of (^mQ³Q²)₈ with helically aligned charges. Thus a type of novel single-stranded nucleic acid transmembrane molecular carriers based on positively charged helical foldamers are introduced. Further, effective and enhanced expression in EGFP-mRNA transfection experiments strongly demonstrates the potential of positively charged foldamers for RNA transmembrane transport and therapy.

Keywords: RNA delivery; electrostatic interactions; helical foldamers; molecular carriers; transmembrane transport.