Safer Gene Therapy Delivery

Advancements in today’s scientific community have increased the abundance of gene therapy treatments. The underlying concept of gene therapy is to replace damaged, missing, or problematic genes with healthy genes using viral vectors.  The problem with this method of disease treatment is that vectors used to deliver gene therapy molecules often undergo spontaneous changes in structure when being manufactured and thus may have altered functionality. Scientists at the University of Pennsylvania are working on techniques to make such compounds more stable thereby making gene therapies safer and more efficient.

The specific viral vector studied during this experiment was the commonly used adeno-associated virus(AAV). It functions by housing the gene of interest in a protein capsule that is the inserted into the nucleus. This study revealed that damage or changes to the viral protein capsule occurs during the manufacturing process and alters its ability to deliver the gene of interest to the appropriate cell type.

 The research team first sought to understand how this capsule functions on a biochemical level. They then worked to stabilize critical points within the capsule to combat mutations that take place before the capsule is used. Research revealed that amide groups of surface-level amino acids  on the vector’s capsule were a main contributing factor to instability. With this knowledge, researchers designed AAV capsules with amide groups removed from side chains for optimal stability. This newly designed vector is estimated to reduce the cost and required dose necessary for gene therapy treatments while improving the overall safety of this technique. Moving forward, this will improve the availability and overall use of gene therapy in battling diseases.