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Sci Rep. 2018 Feb 23;8(1):3556. doi: 10.1038/s41598-018-21863-3.

Nanodelivery of a functional membrane receptor to manipulate cellular phenotype.

Author information

1
University of California Davis, School of Medicine, Department of Biochemistry and Molecular Medicine, Davis, California, USA.
2
University of California Davis, School of Medicine, Department of Pharmacology, Davis, California, USA.
3
Lawrence Livermore National Laboratory, Livermore, California, USA.
4
University of California Davis, Department of Molecular and Cellular Biology, California, USA.
5
VA Northern California Health care system, Mather, California, USA.
6
Lawrence Livermore National Laboratory, Livermore, California, USA. coleman16@llnl.gov.
7
University of California Davis School of Medicine, Radiation Oncology, Sacramento, California, USA. coleman16@llnl.gov.
8
University of California Davis, School of Medicine, Department of Biochemistry and Molecular Medicine, Davis, California, USA. lintian@ucdavis.edu.

Abstract

Modification of membrane receptor makeup is one of the most efficient ways to control input-output signals but is usually achieved by expressing DNA or RNA-encoded proteins or by using other genome-editing methods, which can be technically challenging and produce unwanted side effects. Here we develop and validate a nanodelivery approach to transfer in vitro synthesized, functional membrane receptors into the plasma membrane of living cells. Using β2-adrenergic receptor (β2AR), a prototypical G-protein coupled receptor, as an example, we demonstrated efficient incorporation of a full-length β2AR into a variety of mammalian cells, which imparts pharmacologic control over cellular signaling and affects cellular phenotype in an ex-vivo wound-healing model. Our approach for nanodelivery of functional membrane receptors expands the current toolkit for DNA and RNA-free manipulation of cellular function. We expect this approach to be readily applicable to the synthesis and nanodelivery of other types of GPCRs and membrane receptors, opening new doors for therapeutic development at the intersection between synthetic biology and nanomedicine.

PMID:
29476125
PMCID:
PMC5824837
DOI:
10.1038/s41598-018-21863-3
[Indexed for MEDLINE]
Free PMC Article

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