VP35 small interfering RNA

VP35 small interfering RNA is an RNA interference (RNAi) therapeutic designed to treat Ebola virus infection by targeting the viral VP35 gene. VP35 is a multifunctional protein essential for Ebola virus replication, serving as a critical cofactor for the viral RNA-dependent RNA polymerase complex and acting as a potent antagonist of the host's innate immune response by inhibiting type I interferon production and signaling. The siRNA is typically encapsulated in lipid nanoparticles (LNPs) for systemic delivery. Once inside the host cell, it utilizes the RNA-induced silencing complex (RISC) to mediate the sequence-specific degradation of VP35 mRNA, thereby preventing the synthesis of the VP35 protein. This mechanism effectively halts viral genome replication and restores the host's ability to mount an antiviral response. Developed primarily by Tekmira Pharmaceuticals (now Arbutus Biopharma) in collaboration with the U.S. Department of Defense, this siRNA was a key component of the TKM-Ebola (TKM-100802) and TKM-130803 cocktails, which reached Phase 2 clinical trials before development was discontinued.

Other names

Ebola virus VP35 siRNAsiEBOV-VP35siEBOV-VP-35siEBOV-VP 35