Monogenic diseases stemming from a sole genetic glitch can occur in any organ system. Gene therapy shows the potential to correct these errors. Laboratory-made viruses packed with the appropriate genetic payload have successfully targeted one organ system and cell type after another.
Recent work from scientists from the University of Bristol has successfully shaped viruses known as adeno-associated viruses (AAVs) to treat childhood kidney disease.
The study conducted by Dr. Wen Y. Ding and colleagues focuses on childhood kidney disease, particularly steroid-resistant nephrotic syndrome (SRNS), a potentially deadly non-inherited disorder that can require kidney transplantation. It arises from the mutation of a single gene called NPHS2, which encodes the protein podocin. While purifying our blood by removing waste products, specialized cells in the kidney called podocytes act as crucial filters. However, without a functioning protein podocin, the connective stitching between podocytes becomes leaky and inefficient, contributing to kidney dysfunction.
By perfecting the affinity of AAVs for podocyte cell surface receptors, the researchers believe they successfully transfected these problematic podocytes with the correct genetic material for podocin production. The key was determining the most effective version or serotype of AAV to transduce podocytes. Using mouse models and in vitro human cells, Ding et al. tested various serotypes for their ability to prevent and alleviate kidney disease symptoms.
In the study published in Science Translational Medicine, the AAV-LK03 serotype and podocyte markers colocalized, indicating a successful interaction. Results from both laboratory dish experiments (in vitro) and experiments in living organisms (in vivo) demonstrated a partial alleviation of adhesion problems among podocytes and a reduction in proteinuria—a hallmark of kidney dysfunction. These findings hold immense promise for future clinical applications in treating kidney diseases.
Nonetheless, as with any scientific discovery, further testing is essential before human clinical trials. The next research phase will likely delve into immune responses and potential toxicities associated with this innovative approach. By rigorously addressing these factors, we can move closer to offering a viable treatment option for individuals battling kidney diseases.
Sources: Annual Review of Medicine, Science Translational Medicine