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In this , a drug is monobiotinylated in parallel with the production of a vector/avidin or a vector/strept avidin (SA) fusion protein. The biotinylated drug is produced in one vial and the vector/avid in fusion protein is produced in another vial, and the 2 vials are mixed before administration. Owing to the extremely high affinity of avid in or SA binding of biotin, there is instantaneous capture of thebiotinylatedneurotherapeutic agent by the vector/avid in or vector/SA fusion protein. Monoclonal antibody/avid in andmab/SA fusion genes and fusion proteins are produced with genetic engineering. Brain drug delivery in rats is possible with the OX26 mousemab to the rat tfr. Brain drug delivery in humans is possible with the genetically engineeredchimeric HIRmab. The activity of the genetically engineeredchimeric HIRmab is identical to that of the originalmurine HIRmab and thechimeric antibody is avidly taken up by the primate brain. The brain uptake of the HIRmab in the rhesus monkey is 2% to 4% of the injected dose which is a level of brain uptake that is 1 to 2 log orders greater than the brain uptake of aneuroactive small molecule such as morphine. |
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