Mutant Vesicular Stomatitis Virus Oncolytic Therapy

The patent transforms the static, non-replicating viral vector into a dynamic, replication-competent oncolytic virus that can dynamically multiply within tumor cells. The VSV is engineered to replicate specifically in tumor cells, converting a single-delivery system into a self-amplifying system that progressively increases viral load and infects additional cells over time, thereby resolving the contradiction between reliable gene delivery and limited cell infection percentage.

The oncolytic VSV is designed to be self-replicating within tumor cells, eliminating the need for repeated external administrations. The virus uses the tumor cell's own machinery to replicate and produce new viral particles, which then infect adjacent cells autonomously. This self-service mechanism allows the virus to achieve widespread tumor cell infection without requiring continuous external intervention, resolving the limitation of low infection percentages.

The patent applies local quality by engineering the VSV to have differential replication properties: it replicates efficiently in tumor cells with defective interferon responses but is blocked by functional interferon in normal cells. This creates localized viral activity specifically within the tumor microenvironment, achieving high tumor cell killing effectiveness while sparing normal cells from viral damage and chemotherapy-related side effects.

The patent converts the harmful defect of tumor cells (defective interferon response that allows uncontrolled proliferation) into a beneficial vulnerability that selectively permits viral replication. The interferon-deficient state that enables tumor growth also creates permissiveness for VSV replication, while normal cells with functional interferon responses are protected. This transforms the tumor's pathological characteristic into a selective target for viral therapy, improving tumor cell killing while reducing harm to normal cells.