BLOOD-BRAIN BARRIER VECTOR COMPOUNDS AND CONJUGATES THEREOF

Provided are vector compounds that bind to N-acetylated-alpha-linked acidic dipeptidase-like protein 2 (NAALADL2), and related conjugates, compositions, methods of use thereof, and methods of screening for and identifying the same, for instance, to facilitate delivery of therapeutic or diagnostic agents across the blood-brain barrier (BBB) and/or improve tissue penetration in CNS and peripheral tissues, and thereby treat and/or various diseases, including those of the central nervous system (CNS). 1. A conjugate , comprising: (a) a vector compound that specifically binds to N-acetylated-alpha-linked acidic dipeptidase-like protein 2 (NAALADL2); and (b) a therapeutic or diagnostic agent , where (a) and (b) are covalently or operatively linked to form the conjugate , where the vector compound is not a melanotransferrin (MTf) polypeptide.2. The conjugate of claim 1 , where NAALADL2 is human NAALADL2.3. The conjugate of claim 1 , where NAALADL2 comprises SEQ ID NO:1.4. The conjugate of any of the preceding claims claim 1 , where the vector compound specifically binds to an extracellular domain of NAALADL2.5. The conjugate of claim 4 , where the vector compound specifically binds to a region of residues 143-795 of SEQ ID NO:1.6. The conjugate of any of the preceding claims claim 4 , where vector compound is effective for transporting the therapeutic or diagnostic agent across a blood brain barrier (BBB).7. The conjugate of any of the preceding claims claim 4 , where specific binding of the vector compound to NAALADL2 is effective for transporting the therapeutic or diagnostic agent across a blood brain barrier (BBB).8. The conjugate of any of the preceding claims claim 4 , where the vector compound is a polypeptide or a small molecule.9. The conjugate of claim 8 , where the polypeptide is an antibody or antigen-binding fragment thereof.10. The conjugate of claim 8 , where the polypeptide is a peptide of up to about 50 amino acids in length.11. The conjugate of any of - ...