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Recent progress in the regulation of blood-brain barrier (BBB)

開催日 2014/9/13
時間 15:00 - 17:00
会場 Room E(301)
Chairperson(s) 寺崎 哲也 / Tetsuya Terasaki (東北大学大学院薬学研究科 / Department of Biochemical Pharmacology and Therapeutics, Tohoku University, Japan)
横田 隆徳 / Takanori Yokota (東京医科歯科大学 大学院医歯学総合研究科 脳神経病態学分野 / Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Japan)

Development of BBB-targeting nucleic acid medicine

  • S3-E-2-3
  • 桑原 宏哉 / Hiroya Kuwahara:1 横田 隆徳 / Takanori Yokota: 
  • 1:東京医科歯科大学 大学院医歯学総合研究科 脳神経病態学分野 / Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan 

The development of gene silencing therapy for neurological diseases has placed great importance on the delivery of oligonucleotides, the substances of nucleic acid medicine, from the blood into the brain across the blood-brain barrier (BBB). Increasingly, gene silencing therapy in the BBB itself is being considered because the BBB is associated with the pathophysiologies of many major diseases such as brain ischemia, multiple sclerosis, and neurodegenerative disorders.
Many technical developments have been reported such as the chemical modification of liposomal complexes with oligonucleotides, the direct conjugation of oligonucleotides to ligands for the BBB, and the use of cell-penetrating peptides non-covalently complexed or covalently linked to oligonucleotides. We have developed an efficient delivery system of short-interfering RNA (siRNA) into the BBB along with endogenous lipoprotein. A cholesterol-conjugated siRNA was incorporated into extracted endogenous high-density lipoproteins and then intravenously injected into mice. Cholesterol-conjugated siRNA was not delivered into neurons or glia, but was successfully delivered into the BBB by receptor-mediated uptake. Because cholesterol is taken up into the BBB along with lipoproteins but generally does not pass through the BBB, cholesterol-conjugation might be an effective strategy to deliver siRNA into the BBB.
Endogenous molecule as a ligand can achieve efficient delivery of oligonucleotides into the BBB by utilizing the physiological transport systems. We are now exploring a new technique of utilizing other endogenous molecules for the delivery not only into the BBB but also into the brain across the BBB. In this symposium, we will introduce recent advances and future perspective in the field of delivering nucleic acid medicine into the BBB and also across the BBB.

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