Exosomes Deliver

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Science  29 Apr 2011:
Vol. 332, Issue 6029, pp. 515
DOI: 10.1126/science.332.6029.515-a

Exosomes are small vesicles secreted from cells that can carry proteins and nucleic acids between cells. Alvarez-Erviti et al. have exploited this process to deliver specific RNAs to target cells that lie across a major obstacle: the mammalian blood-brain barrier. Exosomes were isolated from mouse dendritic cells. In order to ensure targeting to the brain, the protein Lamb2b, which is normally expressed by dendritic cells, was tagged with a sequence from rabies viral glycoprotein that binds to a receptor expressed in brain tissue. The exosomes were loaded with small interfering RNA that targets BACE1, a protease that processes β-amyloid protein and produces the aggregates associated with Alzheimer's disease. When injected intravenously into mice, the exosomes crossed the blood-brain barrier and were taken up by brain neurons, oligodendrocytes, and glial cells, thereby decreasing the expression of BACE1 by approximately 60%. Nonspecific uptake of exosomes by other tissues was not observed, nor did the exosomes elicit an adverse immune response. The study suggests that targeted exosomes may have potential value for delivering therapeutic agents into the central nervous system to treat neurodegenerative disorders.

Nat. Biotechnol. 29, 341 (2011).

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