Research Award Recipients

Precision gene editing to disarm BK polyomavirus in kidney transplantation

Lay Abstract

Background: Kidney transplantation offers people with kidney failure a chance to return to healthy, independent living. However, a major complication for kidney transplant recipients remains unsolved: infection by BK polyomavirus (BKV). Most people acquire BKV during childhood, where it remains silent for life, hiding in the kidneys without causing harm. In kidney transplant recipients, the immune system must be suppressed to prevent rejection of the new organ. Unfortunately, this weakened immunity allows BKV to “wake up,” where it can damage the transplanted kidney. As many as 10-15% of kidney transplant recipients develop significant BKV infection, and more than half of those cases lead to loss of the transplanted kidney. There are no medications that specifically target BKV. The only available treatment is to reduce immune-suppressing medications, but this increases the risk of organ rejection.

Purpose: This project aims to create a new strategy to disable BKV by directly cutting its DNA using CRISPR gene-editing technology. Our approach targets two “weak spots” in the virus’s DNA blueprints, one that helps the virus copy itself and another that acts like its main control switch. If either is damaged, the virus cannot fully wake up or make more copies of itself. We will compare different CRISPR tools to find the safest and most powerful way to shut down the virus without harming human cells.

Method: The project will be carried out in three steps. First, we will test different CRISPR designs in kidney cells grown in the lab to see which ones are best at stopping the virus from amplifying itself. We will compare how much virus remains after treatment to find the strongest candidates. Second, we will study the safety of the top-performing CRISPR designs. We will check that they cut only the viral DNA and do not harm human DNA, and we will measure whether the treatment causes any damage to kidney cells. Third, we will test the most promising CRISPR designs in human kidney tissue. In this system, we can experimentally “awaken” the virus, similar to what happens in transplant patients, to see whether our CRISPR treatments effectively eliminate BKV from kidney cells.

Anticipated Outcomes: We expect to find a small number of CRISPR designs that safely and effectively impair BKV. These CRISPR tools should greatly reduce viral replication in kidney cells and should stop the virus from “waking up” in human kidney tissues. We also expect that the best designs will not be harmful to kidney cells. By the end of the project, we aim to have a set of carefully tested CRISPR tools that are strong candidates for the next stage of development.

Patient Engagement: Because this project is focused on early laboratory research, patients are not directly involved in the experiments at this stage. There are no treatment decisions or patient-facing activities yet. However, the direction of the project is strongly shaped by ongoing discussions with transplant doctors who care for people affected by BKV every day. Their experiences and their patients’ needs help guide the goals of this research. As the work moves closer to testing treatments in whole organs and, eventually, in clinical settings, we will include patient partners to help shape the next steps.

Relevance to Patients and Community: For kidney transplant recipients, infection with BKV is one of the most stressful and unpredictable complications they face. Patients often go through repeated blood tests, changes in their medications, and the constant worry that the new kidney might fail. This project directly addresses that worry by working toward the first treatment designed to safely and specifically stop this virus. A therapy like this could reduce the need for frequent monitoring, protect the transplanted kidney, and improve long-term health and quality of life. In the future, this approach could even be used to clear the virus out of donor kidneys before they are transplanted, helping more people receive healthy organs that last longer.

Conclusion: This project introduces a new way to fight one of the most challenging problems in kidney transplantation. By using CRISPR to directly block the virus at its most vulnerable points, we hope to protect transplanted kidneys, help them last longer, and improve the lives of people who depend on them across Canada.