D9-deficient vaccinia virus

D9-deficient vaccinia virus is a genetically engineered form of the vaccinia virus in which the D9 gene (encoding a viral decapping enzyme) has been disrupted or deleted. D9 is one of two poxvirus-encoded decapping enzymes (D9 and D10), both necessary for viral virulence, which remove the protective cap from host and viral mRNAs, promoting their decay and aiding in immune evasion. Loss of D9 disables this decapping activity, leading to increased accumulation of double-stranded RNA (dsRNA), hyperactivation of innate immune response effectors such as PKR and RNase L, and marked viral attenuation in non-tumor tissues. However, tumor cells—often intrinsically deficient in antiviral signaling—remain susceptible to D9-deficient vaccinia virus replication, which provides selective oncolytic activity. Studies in murine and human xenograft models demonstrate tumor-selective replication, significant anti-tumor efficacy, and enhanced immunogenicity compared to wild-type virus. This virus functions as an oncolytic virus (OV) platform with a distinct attenuation profile and is under preclinical development for cancer therapy[1][3][5].

Other names

ΔD9 vaccinia virusdecapping-deficient vaccinia virus (D9)VACV ΔD9