Researchers at Nationwide Children’s Hospital have created a new, improved method of mRNA exon replacement for any disorder through the combination of a transplicing molecule (PTM) and U7 small nuclear RNA constructs exon skipping tool in an AAV vector.

To establish proof of concept, the team tested for mutations in exon 1 and 1 of the SCN2A gene. Two constructs will mediate both exclusions of the endogenous exons 1-2, where one bears a disease-causing mutation, and swaps them with a wild type or enhanced exon 1-2 transplicing molecule. A self-complementary (sc) and/or single stranded adeno-associated virus (AAV) serotypes that target the central nervous system and muscles will deliver the combined approach. These first two products force replacement of mutated SCN2A exon 1-2 for a subpopulation of patients affected by SCN2A disorders.

This combination shows immense potential application in its replacement of any mutated mRNA piece.