Cytoplasmic RNA modulators of an inside-out signal-transduction cascade

A vaccinia virus-based RNA expression system enabled high-level cytoplasmic expression of RNA aptamers directed against the intracellular domain of th e beta 2 integrin LFA-1, a transmembrane protein that mediates cell adhesio n to intercellular adhesion molecule-1 (ICAM-1). In two different cell type s, cytoplasmic expression of integrin-binding aptamers reduced inducible ce ll adhesion to ICAM-1. The aptamers specifically target, and thereby define , a functional cytoplasmic subdomain important for the regulation of cell a dhesion in leukocytes. Our approach of aptamer-controlled blocking of signa ling pathways in vivo could potentially be applied wherever targeted modula tion of a signal transduction cascade is desired.