UC Davis Scientists Develop Highly Targeted AAV Gene Therapy for KSHV-Linked Cancers

DAVIS, Calif. – Oct 1st, 2025 – Scientists at the UC Davis Comprehensive Cancer Center have developed a highly targeted gene therapy that shows promise for revolutionizing the treatment of cancers caused by the Kaposi’s sarcoma-associated herpesvirus (KSHV). The preclinical findings, which demonstrate the therapy’s ability to selectively destroy infected cancer cells with minimal side effects, are set to be published in the December issue of Molecular Therapy Oncology.

The novel strategy addresses cancers like Kaposi’s sarcoma, a major health issue globally, particularly for people living with HIV/AIDS in regions such as sub-Saharan Africa.

“The new strategy uses a specialized gene therapy technique to selectively target and kill cancer cells infected with the virus—while leaving healthy cells unharmed,” said lead author Yoshihiro Izumiya, a professor at UC Davis.

A Smart AAV Virus vs. a Cancer-Causing One
The therapy employs a harmless virus, adeno-associated virus (AAV), as a precise delivery vehicle. This AAV is engineered to act as a genetic “Trojan horse,” delivering a therapeutic payload directly into KSHV-infected cancer cells.

This “smart” AAV gene therapy is designed to become active only in cells harboring KSHV. The activation mechanism relies on a KSHV-specific protein called LANA that acts as a viral marker. Once inside the infected cell, the AAV delivers a gene for a modified thymidine kinase enzyme. This enzyme converts a commonly used anti-herpesvirus drug, ganciclovir, into a potent cancer-killing agent.

“This is a precision-guided approach that uses the virus’s own tricks against it,” Izumiya explained. “It’s like delivering a self-destruct signal directly into the cancer cells.”

Zero Side Effects Observed in Preclinical Models
In laboratory tests using human cells, the AAV-delivered therapy successfully eliminated KSHV-infected cells while leaving uninfected, healthy cells intact. The subsequent studies in mouse models with KSHV-related tumors confirmed the therapy’s potency:

The treatment, when combined with ganciclovir, effectively halted tumor growth.

Importantly, the therapy caused no observable side effects in mice, suggesting a potentially superior safety profile compared to conventional cancer treatments.

Researchers also found that certain anti-cancer drugs that are known to reactivate KSHV could be leveraged to make the AAV gene therapy even more effective by boosting the activation of the delivery system.

While this research is in its early stages, the results offer significant hope for a more precise, less toxic, and potentially personalized treatment path for KSHV-related cancers and possibly other virus-linked malignancies.