Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes

Jiahai Shi, Lenka Kundrat, Novalia Pishesha, Angelina Bilate, Chris Theile, Takeshi Maruyama, Stephanie K. Dougan, Hidde L. Ploegh*, Harvey F. Lodish

*この研究の対応する著者

研究成果査読

116 被引用数 (Scopus)

抄録

We developed modified RBCs to serve as carriers for systemic delivery of a wide array of payloads. These RBCs contain modified proteins on their plasma membrane, which can be labeled in a sortase-catalyzed reaction under native conditions without inflicting damage to the target membrane or cell. Sortase accommodates a wide range of natural and synthetic payloads that allow modification of RBCs with substituents that cannot be encoded genetically. As proof of principle, we demonstrate site-specific conjugation of biotin to in vitro-differentiated mouse erythroblasts as well as to mature mouse RBCs. Thus modified, RBCs remain in the bloodstream for up to 28 d. A single domain antibody attached enzymatically to RBCs enables them to bind specifically to target cells that express the antibody target. We extend these experiments to human RBCs and demonstrate efficient sortase-mediated labeling of in vitro-differentiated human reticulocytes. mammalian cell engineering | sortaggable GPA and Kell | survival time in circulation.

本文言語English
ページ(範囲)10131-10136
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
111
28
DOI
出版ステータスPublished - 2014 7 15
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