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: Compositions and methods for increasing the receptor mediated transport of basic fibroblast growth factor (bFGF) across the blood brain barrier (BBB). The bFGF is conjugated to a BBB targeting agent using either avidin-biotin technology or genetic engineering. The bFGF conjugate was found to cross the BBB at substantially increased rates while still retaining biological activity. In addition, uptake of the bFGF conjugate by non-brain tissue and organs was limited. The bFGF conjugate may be injected intravenously to provide neuroprotection in patients suffering from cerebral stroke.

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: Liposomes containing therapeutic genes are conjugated to multiple targeting agents to provide transport of the encapsulated gene across the blood-retinal barrier and the plasma membrane of ocular cells. Once across the blood-retinal barrier and ocular cell membrane, the encapsulated gene expresses the encoded therapeutic agent within the ocular cells to provide diagnosis and/or treatment of disease.

Abstract: Compositions and methods for increasing the receptor mediated transport of basic fibroblast growth factor (bFGF) across the blood brain barrier (BBB). The bFGF is conjugated to a BBB targeting agent using either avidin-biotin technology or genetic engineering. The bFGF conjugate was found to cross the BBB at substantially increased rates while still retaining biological activity. In addition, uptake of the bFGF conjugate by non-brain tissue and organs was limited. The bFGF conjugate may be injected intravenously to provide neuroprotection in patients suffering from cerebral stroke.

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: Liposomes containing therapeutic genes are conjugated to multiple targeting agents to provide transport of the encapsulated gene across the blood-retinal barrier and the plasma membrane of ocular cells. Once across the blood-retinal barrier and ocular cell membrane, the encapsulated gene expresses the encoded therapeutic agent within the ocular cells to provide diagnosis and/or treatment of disease.

Abstract: Liposomes containing therapeutic genes are conjugated to multiple blood-brain barrier and brain cell membrane targeting agents to provide transport of the encapsulated gene across the blood-brain barrier and brain cell membrane. Once across the blood-brain barrier and brain cell membrane, the encapsulated gene expresses the encoded therapeutic agent within the brain to provide treatment and diagnosis of disease.

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.

Abstract: A method for increasing the transcytosis of an antibody across the microvascular barrier and into the interstitial fluid of organs is disclosed. The method consists of cationizing the antibody with a cationizing agent to increase the isoelectric point of the antibody by between about 1 to about 7 to produce a cationized antibody having an isoelectric point which is less than about 11.5. The increased rate of transport across the microvascular barrier of organs makes such cationized antibodies useful for both therapeutic and diagnostic purposes.

Abstract: The rate of trancytosis of antibodies across the blood-brain barrier is increased by cationizing the antibodies to provide cationized antibodies having an isoelectric point of between about 8.0 to 11.0. The increased rates of transport across the blood-brain barrier makes such cationized antibodies useful for both neurodiagnostic and neuropharmaceutical purposes. Methods for preparing such cationized antibodies are disclosed.

Abstract: A method for quantifying transcytosis through the blood-brain barier by infusing a perfusate into the brain of a living mammal. The perfusate includes a radio-labelled test compound and a radio-labelled marker compound. The perfused brain is removed from the animal and homogenized. The homogenized brain is separated into a microvasculature fraction and a supernatant fraction. The net volume of distribution of the test compound in the supernatant is calculated and corrected to provide an accurate measure of transcytosis through the blood brain barrier.

Abstract: Chimeric peptides adapted for delivering neuropharmaceutical agents, such as neuropeptides into the brain by receptor-mediated transcytosis through the blood-brain barrier. The chimeric peptides include a peptide which by itself is capable of crossing the blood-brain barrier by transcytosis at a relatively high rate. The transportable peptide is conjugated to a hydrophilic neuropeptide which by itself is transportable only at a very low rate into the brain across the blood-brain barrier. The resulting chimeric peptide is transported into the brain at a much higher rate than the neuropeptide alone to thereby provide an effective means for introducing hydrophilic neuropeptides into the brain through the blood-brain barrier.

Abstract: Chimeric peptides adapted for delivering neuropharmaceutical agents, such as neuropeptides into the brain by receptor-mediated transcytosis through the blood-brain barrier. The chimeric peptides include a peptide which by itself is capable of crossing the blood-brain barrier by transcytosis at a relatively high rate. The transportable peptide is conjugated to a hydrophilic neuropeptide which by itself is transportable only at a very low rate into the brain across the blood-brain barrier. The resulting chimeric peptide is transported into the brain at a much higher rate than the neuropeptide alone to thereby provide an effective means for introducing hydrophilic neuropeptides into the brain through the blood-brain barrier.