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

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)10131-10136
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number28
DOIs
Publication statusPublished - 2014 Jul 15
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes'. Together they form a unique fingerprint.

  • Cite this