In 2011, Action Duchenne invested in the first programme of its kind, using adeno-associated virus via triple-transplicing technology, a form of gene therapy, to deliver the full dystrophin gene.  Dr Keith Foster, Reading University, led the project entitled: “Development and evaluation of AAV vectors to restore full length dystrophin to skeletal and cardiac muscle.”

Gene therapy for Duchenne aims to compensate for the lack of dystrophin by transferring the functional dystrophin gene into muscle. Since the DMD gene is the largest gene in the body, delivery of the whole gene is difficult. Shortened versions of the gene have been developed, but full functionality of the protein expressed is compromised as a result of important parts of the protein being missing.

Figure 6 Schematic diagram of triple-hybrid trans-splicing AAV vector system (TTS-AAVs) for expression of full-length dystrophin. The full length codon optimised dystrophin cDNA was cloned into 3 individual AAV vectors such that the reading frame is only re-constituted if there is correct trans-splicing between vector 1, 2 and 3 respectively. (Courtesy of Dr. Keith Foster , Uni. of Reading)

This approach aims to address this problem by dividing the DMD gene into three segments and packaging them into a series of novel gene carriers (known as trans‐spliced adeno-associated virus vectors). The vectors are based on harmless viruses that can carry DNA for delivery to targeted cells within the body. These vectors have been designed so that when used in combination, the different DMD gene segments join together and full length dystrophin protein is expressed (see Figure 6 for more details).

Dr Keith Foster demonstrated proof-of-concept that this methodology can work (data-led evidence that three AAV vectors can be used in concert to deliver full length dystrophin). He started to produce a second-generation viral vector to increase the efficiency of this approach and improve the levels of dystophin expression. He also plans to publish his work in the near future based on the findings of this project that repeat AAV administration results in incremental levels of gene expression.