Gene therapy is a promising method for treating a number of genetic and non-genetic diseases. The most straight forward strategy to treat individuals with deleterious mutations is by inserting a functional version of the gene into the genome. However, the occurrence of vector-related side effects has highlighted the requirement for improved vector designs.
I will explore an up until now ignored possibility of using the naturally occurring recombinases, RAG1 and RAG2, to introduce the wanted transgene into the human immunoglobulin gene loci. These enzymes recognize specific Recombination Signalling Sequences (RSS) that could act as potential integration sites for transgenes.
We are currently in the process of establishing an in vivo assay for testing exogenously expressed Rag1 and Rag2’s ability to execute recombination both on artificial substrate introduced into a B cell line but also directly within the Ig Loci.