shCD59

shCD59 is a short-hairpin RNA (shRNA) therapeutic candidate designed to silence the expression of CD59, a GPI-anchored membrane protein. While CD59's canonical role is the inhibition of the complement system's membrane attack complex, it has been identified as a marker of poor prognosis in acute myeloid leukemia (AML), where it promotes cell survival in a complement-independent manner. By depleting CD59, the therapy alters the protein composition of lipid rafts, specifically increasing the localization of Ras and c-Raf to these domains, which paradoxically prevents the activation of downstream MEK1/2 and ERK1/2. This suppression of the Raf/MEK/ERK signaling pathway leads to G0/G1 cell cycle arrest and increased cell death. Preclinical studies conducted by researchers at the University of Toronto and the Princess Margaret Cancer Centre have demonstrated that shCD59 significantly reduces leukemic burden and extends survival in mouse models of AML.

Other names

short-hairpin RNA against CD59