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 language | English |
|---|---|
| Pages (from-to) | 10131-10136 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 111 |
| Issue number | 28 |
| DOIs | |
| Publication status | Published - 2014 Jul 15 |
| Externally published | Yes |
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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 journal › Article
}
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 -