BLOOD-BRAIN BARRIER DRUG TARGETING: THE FUTURE OF BRAIN DRUG DEVELOPMENT

Outline of a BBB genomics program. Starting with the isolation of brain capillaries (above) from either fresh human brain or animal brain, libraries of brain capillary cDNAs are produced following the initial isolation of brain capillary derived polyA⁺ RNA. Screening for BBB-enriched genes using methodology such as suppressive subtractive hybridization (SSH) leads to classification of genes based on whether the gene function is known or unknown. The genes of unknown function represent about 50% of the detected genes (35, 55, 56). Genes of unknown function consist of uncharacterized genes and gene fragments found in expressed sequence tag (EST) databases. Genes of known function can be categorized into a variety of different gene families as outlined in (35, 55, 56). These genes of known function are selectively enriched at either the rat or human BBB; the names of these known genes are given in full in the original publications (35, 55, 56).