Research press release


Nature Communications

Biotechnology: New peptide escorts therapeutic proteins into the brain


今回、Je-Min Choiたちは、細胞膜を透過し、細胞内にタンパク質や薬物を輸送できる細胞透過性ペプチドの一種を用いたツールを利用して、BBBの克服に成功した。これまでは細胞透過性ペプチドを用いてBBBを効率的に通過することができなかったが、Choiたちが新たに設計したdNP2ペプチドによってそれが可能になった。このdNP2に蛍光タンパク質を結合させて、実験用マウスの脊髄と脳に注入したところ、脊髄と脳が蛍光を発し、dNP2-タンパク質複合体がBBBを通過したことが明らかになった。


Many therapeutics have the potential to effectively treat central nervous system disorders, if only they can cross the blood-brain barrier (BBB) to reach their site of action. A new delivery tool that overcomes this barrier and may potentially help treat multiple sclerosis (MS) is reported in Nature Communications this week. The BBB keeps toxic, infectious and other potentially dangerous substances away from the brain, but it also blocks therapeutic agents and is especially effective at blocking large molecules such as proteins.

Je-Min Choi and colleagues get around this by using a tool belonging to a class of cell-penetrating peptides, which can cross the cell membrane and transport proteins or drugs inside the cell. To date, none of these peptides have been used to efficiently cross the BBB, but the team’s newly designed dNP2 peptide is able to do so. When injected with dNP2 attached to fluorescent protein, the spinal cords and brains of laboratory mice became fluorescent, showing the dNP2-protien complex successfully crossed the BBB.

The authors then attached dNP2 to a fragment of CTLA4, a protein that inhibits lymphocyte activation. Excessive activation of lymphocytes leading to the damage of brain and spinal cord tissues underlies MS. dNP2-CTLA4 treatment was effective in improving health outcomes in a mouse model of MS. These results suggest dNP2 may prove useful in helping to treat neurological disorders ? including MS ? with protein-based therapeutics.

doi: 10.1038/ncomms9244

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