Figure 3.

Intracellular protein therapy with cell‐penetrating (CP) recombinant SOCS3 in metabolically compromised mice challenged with superantigen SEB. A, Conceptual depiction of intracellular delivery of CP‐SOCS3 crossing membrane phospholipid bilayer in energy‐independent process that bypasses endosomal compartment. MTM—membrane‐translocating motif. CP‐SOCS3 targets cytoplasmic tail of IL6 receptor (IL6R) and JAK. B, In vivo delivery of FITC‐labelled CP‐SOCS3 to major organs; (a): CP‐SOCS3 variant with MTM located at the NH₂ terminus of SOCS3. C, Improved survival of mice challenged with superantigen SEB and treated with CP‐SOCS3; (b): CP‐SOCS3 variant with MTM located at the COOH terminus of SOCS3. D, Inflammation‐driven haemorrhagic necrosis and apoptosis of the liver cells in SEB‐challenged mice is suppressed by treatment with CP‐SOCS3 (a) and (b) (adapted from Jo et al, Nat. Med. 2005)