---
_id: '10363'
abstract:
- lang: eng
  text: Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death,
    but its pro-thrombotic activity is problematic for use of erythropoietin in treating
    hypoxia. We constructed a fusion protein that stimulates red blood cell production
    and neuroprotection without triggering platelet production, a marker for thrombosis.
    The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant
    (L108A). The mutation reduces activation of erythropoietin receptor homodimers
    that induce erythropoiesis and thrombosis, but maintains the tissue-protective
    signaling. The binding of the nanobody element to glycophorin A rescues homodimeric
    erythropoietin receptor activation on red blood cell precursors. In a cell proliferation
    assay, the fusion protein is active at 10−14 M, allowing an estimate of the number
    of receptor–ligand complexes needed for signaling. This fusion protein stimulates
    erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity
    in vitro. Our erythropoietin fusion protein presents a novel molecule for treating
    hypoxia.
acknowledgement: This work was supported by funds from the Wyss Institute for Biologically
  Inspired Engineering and the Boston Biomedical Innovation Center (Pilot Award 112475;
  Drive Award U54HL119145). J.L., K.M.K., D.R.B., J.C.W. and P.A.S. were supported
  by the Harvard Medical School Department of Systems Biology. J.C.W. was further
  supported by the Harvard Medical School Laboratory of Systems Pharmacology. A.V.,
  D.R.B. and P.A.S. were further supported by the Wyss Institute for Biologically
  Inspired Engineering. N.G.G. was sponsored by the Army Research Office under Grant
  Number W911NF-17-2-0092. The views and conclusions contained in this document are
  those of the authors and should not be interpreted as representing the official
  policies, either expressed or implied, of the Army Research Office or the U.S. Government.
  The U.S. Government is authorized to reproduce and distribute reprints for Government
  purposes notwithstanding any copyright notation herein. We sincerely thank Amanda
  Graveline and the Wyss Institute at Harvard for their scientific support.
article_number: gzab025
article_processing_charge: No
article_type: original
author:
- first_name: Jungmin
  full_name: Lee, Jungmin
  last_name: Lee
- first_name: Andyna
  full_name: Vernet, Andyna
  last_name: Vernet
- first_name: Nathalie
  full_name: Gruber, Nathalie
  id: 2C9C8316-AA17-11E9-B5C2-8BC2E5697425
  last_name: Gruber
- first_name: Kasia M.
  full_name: Kready, Kasia M.
  last_name: Kready
- first_name: Devin R.
  full_name: Burrill, Devin R.
  last_name: Burrill
- first_name: Jeffrey C.
  full_name: Way, Jeffrey C.
  last_name: Way
- first_name: Pamela A.
  full_name: Silver, Pamela A.
  last_name: Silver
citation:
  ama: Lee J, Vernet A, Gruber N, et al. Rational engineering of an erythropoietin
    fusion protein to treat hypoxia. <i>Protein Engineering, Design and Selection</i>.
    2021;34. doi:<a href="https://doi.org/10.1093/protein/gzab025">10.1093/protein/gzab025</a>
  apa: Lee, J., Vernet, A., Gruber, N., Kready, K. M., Burrill, D. R., Way, J. C.,
    &#38; Silver, P. A. (2021). Rational engineering of an erythropoietin fusion protein
    to treat hypoxia. <i>Protein Engineering, Design and Selection</i>. Oxford University
    Press. <a href="https://doi.org/10.1093/protein/gzab025">https://doi.org/10.1093/protein/gzab025</a>
  chicago: Lee, Jungmin, Andyna Vernet, Nathalie Gruber, Kasia M. Kready, Devin R.
    Burrill, Jeffrey C. Way, and Pamela A. Silver. “Rational Engineering of an Erythropoietin
    Fusion Protein to Treat Hypoxia.” <i>Protein Engineering, Design and Selection</i>.
    Oxford University Press, 2021. <a href="https://doi.org/10.1093/protein/gzab025">https://doi.org/10.1093/protein/gzab025</a>.
  ieee: J. Lee <i>et al.</i>, “Rational engineering of an erythropoietin fusion protein
    to treat hypoxia,” <i>Protein Engineering, Design and Selection</i>, vol. 34.
    Oxford University Press, 2021.
  ista: Lee J, Vernet A, Gruber N, Kready KM, Burrill DR, Way JC, Silver PA. 2021.
    Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein
    Engineering, Design and Selection. 34, gzab025.
  mla: Lee, Jungmin, et al. “Rational Engineering of an Erythropoietin Fusion Protein
    to Treat Hypoxia.” <i>Protein Engineering, Design and Selection</i>, vol. 34,
    gzab025, Oxford University Press, 2021, doi:<a href="https://doi.org/10.1093/protein/gzab025">10.1093/protein/gzab025</a>.
  short: J. Lee, A. Vernet, N. Gruber, K.M. Kready, D.R. Burrill, J.C. Way, P.A. Silver,
    Protein Engineering, Design and Selection 34 (2021).
date_created: 2021-11-28T23:01:28Z
date_published: 2021-11-01T00:00:00Z
date_updated: 2023-08-14T13:01:38Z
day: '01'
department:
- _id: CaGu
doi: 10.1093/protein/gzab025
external_id:
  isi:
  - '000746596900001'
  pmid:
  - '34725710'
intvolume: '        34'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1093/protein/gzab025
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
publication: Protein Engineering, Design and Selection
publication_identifier:
  eissn:
  - 1741-0134
  issn:
  - 1741-0126
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Rational engineering of an erythropoietin fusion protein to treat hypoxia
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 34
year: '2021'
...