Gene therapy is beginning to deliver on its immense therapeutic promise as exemplified by the successful treatment of infants with spinal muscular atrophy using vectors based on adeno-associated virus serotype 9 (AAV9; Zolgensma^TM).

The potential for using gene therapy in the treatment of rare kidney diseases using AAV are numerous, although most of these approaches are dependent on successful uptake of the AAV by kidney cells, which is proving challenging. Indeed, some of the research in the Complement Therapeutic Research Group is moving towards gene therapy of the liver to act as a factory to produce proteins that protect the kidney.

One approach is to instruct the liver to make antibodies (proteins belonging to the immune system that normally target infectious agents, like bacteria and viruses) against a molecule called C7. C7 is part of the complement system.

The complement system is often involved in kidney disease, particularly the last part of the complement cascade which can punch holes in kidney cells, leading to their death. By producing anti-C7 proteins in the liver, and delivery through the blood stream, we can prevent damage to the kidney.

Through use of gene therapy, we can give this once to patients and the treatment may last a lifetime, that may have increased risk of infections so we can adapt the approach to allow the anti-C7 proteins to be switch off and back on only when needed.

Overall, we hope this approach will be cheaper and safer than existing medicines and approaches. If successful, there are several other situations that the anti-C7 gene therapy might be used.