09.2018 | THE SCIENTIST 35© GEORGE RETSECK
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eleased from almost all cell types, found in blood and other
bodily fluids, and thought to play a role in cell-to-cell communi-
cation, the tiny vesicles called exosomes are garnering a great
deal of research interest both as potential diagnostic tools and as vehi-
cles for drug delivery. Many researchers are developing methods for
capturing, modifying, and tissue-targeting exosomes. One such tool—
the protein CP05—may accomplish all three.
Haifang Yin of Tianjin Medical University in China and colleagues
discovered CP05 in a search for proteins that bind CD63—a trans-
membrane protein abundant on the surface of exosomes. They’ve used
this interaction to not only isolate exosomes from human serum via
CP05-coated magnetic beads, but also to load cargo onto exosomes
and send them to various tissues in mice.
To accomplish the latter, the team created peptide chimeras of CP05
with the tissue-targeting peptides M12, RVG, or SP94 to direct exo-
somes to muscle, brain, or subcutaneous tumors, respectively. They also
delivered an oligomer that corrects a splicing error in dystrophin to the
muscles of mdx mice (which display the murine equivalent of Duchenne
muscular dystrophy symptoms). Both expression of functional dystro-
phin protein and the grip strength of the animals increased.
The use of CP05 is “an interesting concept,” says Pieter Vader of
the University Medical Center Utrecht, in the Netherlands, because
“it circumvents the whole issue of having to engineer cells.” Producing
exosomes targeted to specific tissues usually involves genetic engi-
neering of the cells from which the exosomes are to be collected, Vader
explains. But with Yin’s system, “[you] just click something on that
steers exosomes toward certain tissues.”
While the results of the targeting experiments are “very impres-
sive,” adds Vader, who was not involved with the research, it’s unclear
whether the CP05-coated magnetic beads would be preferable toexisting methods for isolating exosomes, such as centrifugation, size
exclusion chromatography, and immunoaffinity.
“What we have is a technology that can deliver cargo specifically in
vivo,” says Yin. The next step is “to partner with researchers who have
specific therapeutic cargoes for specific diseases to see if we can help
them.” (Sci Transl Med, 10:eaat0195, 2018)gAT A GLANCEWith CP05
peptideA chimeric peptide consisting of
CP05 and a tissue-targeting peptide
is incubated with exosomes and binds
to the membrane protein CD63.CP05 is conjugated to the
cargo molecule and incu-
bated with exosomes at the
same time as the tissue-tar-
geting chimeric peptide.Researchers identify a handy exosome-binding tool
for tinkering with the versatile vesicles.BY RUTH WILLIAMSExosome Engineering
MODUS OPERANDIBrain, muscle, tumor Sci Transl Med, 10:eaat0195, 2018EXOSOME
MODIFICATIONTISSUE TARGETING METHOD CARGO LOADING TISSUES TARGETED
IN VIVOREFERENCESGenetic
engineeringCells are engineered to express a fusion
protein consisting of an exosomal mem-
brane protein and a tissue-targeting pep-
tide. Exosomes displaying the fusion pro-
tein are then collected from the cells.The cargo molecule is
transfected either into the
engineered cells or into
the exosomes directly.Brain, tumor Nat Biotechnol, 29:341–45, 2011Theranostics, 7:1333–45, 2017TISSUE-TARGETED THERAPEUTIC EXOSOMES: To treat a mouse model
of Duchenne muscular dystrophy, molecules of the exosome-binding pep-
tide CP05 are linked either to the muscle-targeting peptide M12 or an
oligomer (PMO) that corrects a splicing error in the gene for dystrophin.
These two conjugate peptides paint the surface of exosomes from cultured
mouse cells. When injected into the mice, the exosomes home to muscle,
where they deliver the oligomer, boost functional dystrophin levels,
and improve muscle function.CP05 + M12CP05 + PMOExosomeDuchenne muscular dystrophy model Treated mouse