Abstract: The invention provides diagnostic and therapeutic macromolecular compositions that cross the blood-brain barrier, in some embodiments in both directions, while allowing their activity to remain substantially intact once across the barrier. Also provided are methods for using such compositions in the diagnosis or treatment of CNS disorders such as Alzheimer's disease.

Abstract: Provided herein are compositions for increasing transport of agents across the blood-brain barrier, in some embodiments in both directions, while allowing their activity once across the barrier to remain substantially intact. The agents are transported across the blood-brain barrier via one or more endogenous receptor-mediated transport systems. In some embodiments the agents are therapeutic, diagnostic, or research agent. Also provided herein are nucleic acids encoding proteins contained in the compositions.

Abstract: A humanized murine antibody is provided that binds to the human insulin receptor (HIR). The humanized murine antibody is suitable for use as a Trojan horse to deliver pharmaceutical agents to human organs and tissue that express the HIR. The humanized munne antibody is especially well suited for delivering neuropharmaceutical agents from the blood stream to the brain across the blood brain barrier (BBB). The humanized murine antibody may be genetically fused to the pharmaceutical agent or it may be linked to the pharmaceutical agent using an avidin-biotin conjugation system.

Abstract: A humanized murine antibody is provided that binds to the human insulin receptor (HIR). The humanized murine antibody is suitable for use as a Trojan horse to deliver pharmaceutical agents to human organs and tissue that express the HIR. The humanized murine antibody is especially well suited for delivering neuropharmaceutical agents from the blood stream to the brain across the blood brain barrier (BBB). The humanized murine antibody may be genetically fused to the pharmaceutical agent or it may be linked to the pharmaceutical agent using an avidin-biotin conjugation system.

Abstract: This invention provides imaging reagents for the detection of a gene or gene expression product (e.g. mRNA) in a brain cell in vivo. Preferred reagents comprise a detectable label attached to a first nucleic acid that specifically hybridizes to the gene or to a nucleic acid transcribed from the gene. The first nucleic acid is linked to a targeting ligand that is capable of binding a receptor on a cell comprising the blood brain barrier and crossing said blood brain barrier.

Abstract: A composition for delivering an agent to cells in vitro or to tissues or organs in vivo. The composition comprises either avidin or an avidin fusion protein bonded to a biotinylated agent to form an avidin-biotin-agent complex. A method is further provided for delivering an agent to cells using the avidin-biotin-agent complex which involves administering the complex to an individual subject. The avidin-biotin-agent complex is used in therapeutic and diagnostic methods.