Biology Reference
In-Depth Information
database (
http://exocarta.ludwig.edu.au
)
. The protein content of exosomes has been
extensively analyzed by mass spectrometry-based proteomic studies or by western
blotting. The content of exosomes may vary depending on their source. Some pro-
teins are relatively abundant in all exosomes, such as Alix, TSG101, LAMP1,
HSP70 and the tetraspanins CD63, CD81, and CD9 [
65
] and are thus frequently
used as markers for exosome characterization. One class of cytosolic proteins com-
monly detected in exosomes includes the Rabs, which regulate exosome docking
and membrane fusion, and annexins which aid in membrane trafficking and fusion
[
66
]. Exosomes also contain cell-type-specific proteins such as A33, MHC II, CD86,
and MFG-E8/lactadherin [
66
]. Other exosomal proteins include the metabolic
enzymes, ribosomal proteins, transmembrane, signal transduction, adhesion,
ATPases, cytoskeletal, and ubiquitin molecules [
67
]. In addition, the lipid composi-
tion of exosomes is characteristic of the cell origin and plays a critical role in exo-
some biogenesis [
68
] .
MVs also contain genetic material in the form of mRNA and microRNA that may
allow easy screening for disease genetic markers and offer new diagnostic and prog-
nostic information [
69
]. The messages transmitted by intercellular communication
may include those for survival, growth, division, differentiation, stress responses,
apoptosis, etc. In addition, exosomes are present in body fluids such as saliva, urine,
breast milk, and blood plasma, which are conveniently available from patients. For
example, the discovery of microRNA in human salivary samples suggests a promis-
ing use of salivary exosomes as biomarkers for disease diagnosis. Hence, the hori-
zontal transfer of RNA offers a new perspective on intercellular communication and
has potential therapeutic applications, for example, in gene delivery [
66
] .
9.4
Membrane Vesicles: Opportunities for RNAi
Therapeutic Delivery and Insights into RNAi Biology
The multifunctionality of membrane vesicles in cellular transport and signaling
underlies their potential as a valuable therapeutic resource. However, this potential
is only just beginning to be unraveled. In this section, we will discuss the unique
properties that render exosomes particularly useful in RNAi therapeutics and
describe the seminal studies to first exploit exosomes in this context and the advan-
tages of exosomes over existing RNAi delivery strategies. We will also highlight
current and foreseeable obstacles in the route to full clinical translation of mem-
brane vesicles in RNAi therapeutics.
9.4.1
Exosomes Possess Unique Properties That Render
Them Useful for RNAi Therapeutics
Since they were first described in sheep reticulocytes [
70
], our knowledge of the
biological functions of exosomes has been expanding, fuelling interest both in the
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