RNApatch Production For mRNA Delivery

Seattle Genova also provides mRNA-loaded dissolving microneedles (RNApatch) technology. This technique is fabricated using the micromolding method followed by physical and functional characterization. The RNApatch is mechanically strong and is capable of mediating cutaneous delivery of naked mRNA. Transfection efficiency and kinetics improved with increased RNApatch needle lengths and are comparable with subcutaneous injection. RNApatch is a viable delivery platform for mRNA and represents an attractive option with significant translation potential for the delivery of mRNA therapeutics. A key advantage of delivering mRNA via the dissolvable microneedle platform is that it is delivered in solid form and hence obviates the need for handling mRNA in solution form, which not only avoids product damage caused by RNase contamination but also improves mRNA shelf life.

Mechanism

In vitro transcribed messenger RNA (mRNA) loaded in a dissolving microneedle patch (RNApatch). Low molecular weight polyvinylpyrrolidone (PVP) is selected because the excipient because it is a clinically permitted polymer that possesses excessive mechanical strength, biocompatibility and water solubility. In addition, PVP is a synthetically derived material, which reduces the probability of RNase contamination at source. (PVP) can directly be used without further purification for RNApatch fabrication with no detectable mRNA degradation. Physical and functional integrity of mRNA saved in the RNApatch are absolutely preserved for at least 2 weeks under ambient conditions. While the loading of mRNA into RNApatch is constrained via way of means of the solubility of mRNA in concentrated PVP solution, mechanical strength of RNApatch is not compromised by the presence of mRNA. RNApatch can mediate in vivo transgene expression of mRNA encoding luciferase for up to 72 hours and transfection efficiency and kinetics mediated through RNApatch compares favorably to subcutaneous injection. Interestingly, mRNA transfection efficiency does not correlate with contact surface area however instead it will increase with deeper delivery depths.

Highlights