An RNA Alternative to Human Transferrin: A New Tool for Targeting Human Cells

作者：Wilner Samantha E; Wengerter Brian; Maier Keith; Borba Magalhaes Maria de Lourdes; Del Amo David Soriano; Pai Supriya; Opazo Felipe; Rizzoli Silvio O; Yan Amy; Levy Matthew^*

来源：Molecular Therapy - Nucleic Acids, 2012, 1: e21.

DOI：10.1038/mtna.2012.14

The transferrin receptor, CD71, is an attractive target for drug development because of its high expression on a number of cancer cell lines and the blood brain barrier. To generate serum-stabilized aptamers that recognize the human transferrin receptor, we have modified the traditional aptamer selection protocol by employing a functional selection step that enriches for RNA molecules which bind the target receptor and are internalized by cells. Selected aptamers were specific for the human receptor, rapidly endocytosed by cells and shared a common core structure. A minimized variant was found to compete with the natural ligand, transferrin, for receptor binding and cell uptake, but performed similar to twofold better than it in competition experiments. Using this molecule, we generated aptamer-targeted siRNA-laden liposomes. Aptamer targeting enhanced both uptake and target gene knockdown in cells grown in culture when compared to nonmodified or nontargeted liposomes. The aptamer should prove useful as a surrogate for transferrin in many applications including cell imaging and targeted drug delivery.

• 出版日期2012-5