New approach to gene therapy

The New Approach to gene editing using the CRISPR/Cas9 system bypasses disease-causing mutations in a, enabling treatment of genetic diseases linked to a single gene, such as cystic fibrosis, certain types of sickle cell anemia, and other rare diseases. This method, developed and tested in mice and human tissue cultures by researchers at Penn State, involves inserting a new, fully functional copy of the that displaces the mutated. This study was published in the journal Molecular Therapy.

The CRISPR system is pledging new gene therapies that can target and correct disease-causing mutations in a gene. Cas9 is a bacterial protein that cuts DNA at a specific location, where the sequence can then be edited, trimmed, or a new sequence inserted before the DNA is repaired.

There are two main limitations to current repair strategies. First, the common repair strategy, called homology-directed repair, requires using specific proteins within the cell that are only present during cell division, which means the repair process cannot be used in most adult tissues where cell division occurs rarely.

Douglas Cavener, professor of biology at Penn State and senior author of the paper said that the second challenge stems from the fact that even when a disease is caused by a single, it can result from a variety of different mutations within that. The homology-directed repair, they need to design and test the strategy for every one of those mutations, which can be expensive and time-intensive. In this study, we designed an approach called Co-opting Regulation Bypass Repair which can be used in both dividing and non-dividing cells and tissues and for a spectrum of mutations within a gene. This method is promising for rare diseases caused by a single, where limited time and resources typically preclude design and testing for the many possible disease-causing mutations.