Scientists at KU Leuven affiliated to VIB, the Flemish life sciences research institute, and Cellectis, the French genome engineering specialist, have announced they are to collaborate on research into new gene therapy approaches to cure haemophilia.
Thierry Vandendriessche and Marinee Chuah from the VIB Vesalius Research Centre at KU Leuven will use meganucleases – tailor-made enzymes engineered by Cellectis – to replace faulty blood clotting factor genes with functional copies.
Haemophilia is a group of hereditary, recessive, sex-linked genetic disorders that impair the body’s ability to control blood clotting or coagulation. Haemophilia A (Factor VIII deficiency) is the most common form of the disorder, occurring in around 1 in 5,000 -10,000 male births. Haemophilia B (Factor IX deficiency) occurs at about 1 in about 20,000-34,000 male births.
Haemophilia patients suffer in various degrees from uncontrolled internal and external bleeding after a blood vessel is broken. In areas such as the brain or inside joints, this bleeding can be fatal, or permanently debilitating.
Genetic therapy has long been considered a rational approach to cure haemophilia. However, one of the major setbacks to date was that new genetic material was inserted anywhere into the DNA, possibly disrupting useful genes, leading to unwanted side effects or the lack of expression of the gene of interest. Cellectis’ meganuclease technology enables accurate insertion of functional copies of the Factor VIII and Factor IX genes in a way that does not disturb the other functions of the targeted cell.
“Meganucleases have the potential to solve the random insertion issue,” commented Vandendriessche and Chuah.