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Mol Ther Nucleic Acids. 2013 Jan 8;2:e67. doi: 10.1038/mtna.2012.59.

In vivo SELEX for Identification of Brain-penetrating Aptamers.

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1
Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.

Abstract

The physiological barriers of the brain impair drug delivery for treatment of many neurological disorders. One delivery approach that has not been investigated for their ability to penetrate the brain is RNA-based aptamers. These molecules can impart delivery to peripheral tissues and circulating immune cells, where they act as ligand mimics or can be modified to carry payloads. We developed a library of aptamers and an in vivo evolution protocol to determine whether specific aptamers could be identified that would home to the brain after injection into the peripheral vasculature. Unlike biopanning with recombinant bacteriophage libraries, we found that the aptamer library employed here required more than 15 rounds of in vivo selection for convergence to specific sequences. The aptamer species identified through this approach bound to brain capillary endothelia and penetrated into the parenchyma. The methods described may find general utility for targeting various payloads to the brain.Molecular Therapy - Nucleic Acids (2013) 2, e67; doi:10.1038/mtna.2012.59; published online 8 January 2013.

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