The present invention relates to peptides that bind with high specificity and which functionally interact with the
transferrin receptor (“TfR”) and which may be used in making molecular vehicles that carry biomolecules across membranes, including, e.g., across the
blood brain barrier or the
gastrointestinal tract. TfR specific binding moieties may also be used alone or as components in specific molecules that target the
transferrin /
transferrin receptor transport system. The invention relates more specifically to VNAR
single chain antibodies derived from nurse shark that bind to TfR, compounds and compositions comprising a TfR specific VNAR binding
moiety, methods for preparing them, diagnostic and therapeutic methods of use
in vitro or
in vivo, e.g., to diagnose, treat and / or prevent a
pathological condition, disorder or
disease in which it is beneficial to deliver a
heterologous biomolecule across the
blood brain barrier by association with a TfR specific VNAR binding
moiety. Other uses for TfR specific VNAR binding moieties of the invention include, e.g., regulating the interaction of iron-charged transferrin with TfR (
receptor cycling or
cell surface presentation), such as may be therapeutic in treatment of certain
cancer cells and tumors of various tissue types.