Research ArticleDrug Development

Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation

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Science Translational Medicine  23 Nov 2016:
Vol. 8, Issue 366, pp. 366ra162
DOI: 10.1126/scitranslmed.aaf8463

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Tackling a tough target: An ATP-sensitive channel

Injured and dying cells release lots of ATP, which triggers inflammation by binding to the ion channel P2X7. Interfering with this process could treat numerous diseases, but so far small-molecule drugs have not been potent or specific enough. Now, Danquah and colleagues have developed single-domain “mini antibodies” called nanobodies that rise to the challenge. One of their nanobodies blocked the P2X7 channel and inhibited disease in mouse models of kidney inflammation and contact dermatitis. Another nanobody dampened the release of inflammatory messengers from human cells 1000 times more effectively than the small-molecule drugs now under development. Nanobodies can be linked together to prolong their lifetime or confer cell specificity, a useful versatility that increases their appeal.