Next-generation bioengineered viruses for muscle gene therapy
News | BioQuant | September 23rd, 2022
Human gene therapy is an advanced form of biomedicine that promises to cure human diseases with an inherited or acquired genetic cause at their root. Typically, this is achieved by using so-called "vectors" (gene transfer vehicles) to add those genes that are missing or defect in cells in the body. A particular challenge is posed by diseases that affect the human striated musculature, such as Duchenne muscular dystrophy (DMD), considering the need to concurrently target vectors to the skeletal muscle, heart and diaphragm, ideally via non-invasive administration.
As now reported by the lab of Prof. Dirk Grimm in Science Advances, this can be achieved through bioengineering of the capsid (protein shell) of Adeno-associated viruses (AAV). Using their portfolio of powerful technologies including DNA shuffling, viral peptide display, DNA/RNA barcoding and deep sequencing, the group has successfully created AAV vectors that effectively and specifically deliver therapeutic genes to the entire striated musculature in vivo. As shown in two mouse models of DMD or X-linked myotubular myopathy, these novel vectors can ameliorate disease symptoms from a single, minimally invasive injection into the circulation. This highlights their great potential for future translation into human patients suffering from devastating, currently intractable and often life-threatening muscle disorders.
This work was conducted within the EU-funded research consortium MYOCURE and was spearheaded in Prof. Grimm's lab in BioQuant by Dr. Josef El Andari, with further seminal contributions by his team members Dr. Jonas Weinmann, Dr. Julia Fakhiri, Chiara Krämer and Ellen Wiedtke.
Andari et al., Science Advances 2022: https://pubmed.ncbi.nlm.nih.gov/36129972/
Grimm lab website: https://grimm-labs.com/
Grimm lab @Twitter: https://twitter.com/grimmlab