Unlocking the potential of cell-permeable nanobodies for intracellular applications

Delivering functional nanobodies intracellularly is a powerful method for studying cellular pathways and tracking protein dynamics in live cells. Recently, the field has advanced towards interrogating pathological targets to modulate cellular function. This review summarises current research employing diverse strategies for cellular uptake of nanobodies and subsequent antigen recognition. We specifically emphasise the potential of cell-permeable nanobodies as functional therapeutics in relevant diseases, such as cancer, respiratory diseases and neurological disorders. Lastly, we discuss the current challenges, translational clinical efforts and future perspectives for cell-permeable nanobodies.