Fig. 1.

Routes into the cell for antibodies. Antibodies can be expressed in cells or delivered as proteins to cells. Antibodies fold correctly in the endoplasmic reticulum (ER), where they are naturally expressed, as well as in mitochondria. The expression of antibodies in the cytosol may require selection for antibodies that are suitable for folding in the cytosol (dashed lines) using one of the cytosolic intrabody selection technologies. Antibodies can be delivered as proteins to the cytosol, for instance, by physical methods that are associated with membrane disruption. The critical step for antibodies that are delivered via a route that involves endosomal uptake is overcoming endosomal entrapment, which has been a major efficiency bottleneck for some of those approaches. The delivery of antibodies to the lysosome can serve to deliver small molecules to the cytosol of selected cell types, such as in antibody–drug conjugates (ADCs). Small protein toxins or peptides have been delivered to the cytosol via retrotranslocation from the ER to the cytosol