Developing kidney models to test and develop new therapies to prevent kidney damage by BK virus in transplant patients
Professor Colin Crump from the University of Cambridge is looking for new ways to prevent kidney damage caused by BK virus and is developing models of mini kidneys to test potential treatments for the BK virus in the lab.
The challenge of BK Virus for kidney transplant recipients
BK virus is a common virus that nearly everyone picks up in childhood, generally without noticing. Once you have been infected with BK virus, it can hide in the kidneys without causing obvious symptoms. Reactivation of BK virus can happen in kidney transplant recipients due to immunosuppressive medications, these drugs prevent the immune system from attacking the new kidney, but they also make it harder to fight infections such as BK virus.
When BK virus reactivates in this setting, it can cause polyomavirus-associated nephropathy (PVAN), a condition that damages the transplanted kidney.
Currently there are no specific treatments for BK virus or its complications. Reducing immunosuppressive medication helps the immune system to fight BK virus, but it carries the risk that the immune system might damage the transplanted kidney.
How can we target the BK virus?
It is difficult to target the BK virus directly because it makes very few proteins that drugs can aim for. Like all viruses, BK relies on human cells to reproduce, so by identifying which “tools” inside the cell the virus depends on, researchers may be able to stop BK infection without harming the kidney.
To look into this, Colin and the team used a powerful gene-editing technique called CRISPR.
CRISPR acts like a pair of molecular scissors, allowing scientists to switch off individual genes in a cell and see what happens. By turning off genes one by one, they could find out which ones the virus needs to survive.
One key gene they found makes an enzyme called MAT2A. When MAT2A is blocked, either by switching the gene off or using a drug, the virus struggles to make new copies of itself.
Growing miniature kidneys in the lab to test treatments
Colin and the team at Cambridge are developing “kidney organoids” - these are tiny, 3D miniature kidneys.
They contain all the main cell types of a human kidney nephron (the tiny filtration unit of the kidney) and can be infected by BK virus, providing a realistic way to study it.
“By using kidney organoids, we can monitor how the virus spreads, and test whether drugs targeting MAT2A, or other promising targets can stop it. This gives us a powerful way to explore new treatments for protecting transplanted kidneys.” Professor Colin Crump.
What could this mean for kidney transplant patients?
This research could pave the way for new therapies to protect transplanted kidneys from BK virus, helping them last longer.
David Crosby, chief research officer at Kidney Research UK commented: “By combining cutting-edge gene editing with innovative kidney models, Professor Colin Crump’s team is opening new ways to understand and tackle BK virus where current treatments fall short. We are proud to fund research with the potential to protect transplanted kidneys and improve outcomes for patients.”
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