La Sapienza University out-licenses exon-skipping technology

Licensing deal

Gene therapy specialist Amsterdam Molecular Therapeutics has obtained a license from La Sapienza University in Rome, Italy, to small nuclear RNA-based exon-skipping technology for the treatment of Duchenne muscular dystrophy (DMD). The company intends to combine the technology with its adeno-associated virus gene therapy platform, to potentially create a long-term treatment for this seriously debilitating disease.

DMD is caused by mutations in the dystrophin gene, which is the largest known human gene. Dystrophin is essential for muscle function, and inability to produce it leads to severely debilitating neuromuscular disease and death in young adulthood. Around 120,000 people suffer from the disease in the US and Europe, and there is no treatment.

A group led by Irene Bozzoni at La Sapienza is developing a treatment for DMD using adeno-associated viral vectors and an exon-skipping small nuclear RNA construct. The researchers have shown a long-term systemic and therapeutic effect in animal models after a single administration.

Exon skipping is a technology that aims to neutralise genetic defects by preventing the faulty parts of the gene from being activated. At the cellular level, messenger RNA reads off, or transcribes, the protein instructions from the gene. It then transports these instructions to the ribosomes in the cell where the protein is assembled.

Messenger RNA is not a transcript of the complete gene sequence, but only of the exons, which are the sections of the gene that code for a portion of the protein. If one of the exons contains an error, this process may be halted, and the production of the full-length dystrophin protein cannot take place. But when the faulty exon is skipped, protein synthesis does take place and leads to a functional, albeit shorter, dystrophin protein. By using the exon-skipping technique the mutated exons in the dystrophin  messenger RNA that contain errors are “skipped” and as a result the muscle cells are able to produce functional dystrophin protein.