lentivirus-expressing dominant-negative tumor necrosis factor

Lentivirus-expressing dominant-negative tumor necrosis factor (lenti-DN-TNF) is an experimental gene therapy designed to provide neuroprotection in Parkinson's disease. It utilizes a self-inactivating lentiviral vector to deliver the genetic sequence for a dominant-negative variant of tumor necrosis factor (TNF), specifically the XENP345 protein (containing A145R/I97T mutations). Once expressed and secreted, the dominant-negative TNF subunits exchange with native soluble TNF (sTNF) monomers to form inactive heterotrimers, thereby selectively neutralizing sTNF signaling without affecting transmembrane TNF. This approach aims to attenuate neuroinflammation and dopaminergic neuron loss in the substantia nigra, as demonstrated in preclinical rat models of Parkinson's disease.

Other names

lenti-XENP345lenti-XENP-345lenti-XENP 345lentiviral dominant-negative TNFlentiviral DN-TNF