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

76 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

Fingerprint

Single-Domain Antibodies
Erythrocytes
Cell Membrane
Cell Engineering
Erythroblasts
Reticulocytes
Biotin
Survival
Antibodies
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • General

Cite this

Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes. / Shi, Jiahai; Kundrat, Lenka; Pishesha, Novalia; Bilate, Angelina; Theile, Chris; Maruyama, Takeshi; Dougan, Stephanie K.; Ploegh, Hidde L.; Lodish, Harvey F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 28, 15.07.2014, p. 10131-10136.

Research output: Contribution to journalArticle

Shi, Jiahai ; Kundrat, Lenka ; Pishesha, Novalia ; Bilate, Angelina ; Theile, Chris ; Maruyama, Takeshi ; Dougan, Stephanie K. ; Ploegh, Hidde L. ; Lodish, Harvey F. / Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 28. pp. 10131-10136.
@article{89c1647124004dc69529ef537051ca66,
title = "Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes",
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.",
author = "Jiahai Shi and Lenka Kundrat and Novalia Pishesha and Angelina Bilate and Chris Theile and Takeshi Maruyama and Dougan, {Stephanie K.} and Ploegh, {Hidde L.} and Lodish, {Harvey F.}",
year = "2014",
month = "7",
day = "15",
doi = "10.1073/pnas.1409861111",
language = "English",
volume = "111",
pages = "10131--10136",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "28",

}

TY - JOUR

T1 - Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes

AU - Shi, Jiahai

AU - Kundrat, Lenka

AU - Pishesha, Novalia

AU - Bilate, Angelina

AU - Theile, Chris

AU - Maruyama, Takeshi

AU - Dougan, Stephanie K.

AU - Ploegh, Hidde L.

AU - Lodish, Harvey F.

PY - 2014/7/15

Y1 - 2014/7/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84904284885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904284885&partnerID=8YFLogxK

U2 - 10.1073/pnas.1409861111

DO - 10.1073/pnas.1409861111

M3 - Article

C2 - 24982154

AN - SCOPUS:84904284885

VL - 111

SP - 10131

EP - 10136

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 28

ER -