Hybridization Networks of mRNA and Branched RNA Hybrids

Abstract

Messenger RNA (mRNA) is emerging as an attractive biopolymer for therapy and vaccination. To become suitable for vaccination, mRNA is usually converted to a biomaterial, using cationic peptides, polymers or lipids. An alternative form of converting mRNA into a material is demonstrated that uses branched oligoribonucleotide hybrids with the ability to hybridize with one or more regions of the mRNA sequence. Two such hybrids with hexamer arms and adamantane tetraol as branching element were prepared by solution‐phase synthesis. When a rabies mRNA was treated with the branched hybrids at 1 M NaCl concentration, biomaterials formed that contained both of the nucleic acids. These results show that branched oligoribonucleotides are an alternative to the often toxic reagents commonly used to formulate mRNA for medical applications.

Caging of a Strongly Pairing Fluorescent Thymidine Analog with Soft Nucleophiles

“…In order to have a strong enough effect upon reaction with intracellular nucleophiles, carrier strands with several J residues may be used. The cargo strands may be therapeutically active oligonucleotides like antisense or antigen oligonucleotides or possibly mRNAs hybridized to multiple carrier oligonucleotides [46] . An efficient release process appears realistic because the concentration of free glutathione is low outside the cell, but it is abundant inside the cell, [47] so that rapid intracellular release by addition to J is conceivable.…”