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2016 ; 36
(3
): 417-27
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Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential
Treatments for Parkinson s Disease, Glioma, and Schwannoma
#MMPMID27017608
Hall J
; Prabhakar S
; Balaj L
; Lai CP
; Cerione RA
; Breakefield XO
Cell Mol Neurobiol
2016[Apr]; 36
(3
): 417-27
PMID27017608
show ga
Extracellular vesicles present an attractive delivery vehicle for therapeutic
proteins. They intrinsically contain many proteins which can provide information
to other cells. Advantages include reduced immune reactivity, especially if
derived from the same host, stability in biologic fluids, and ability to target
uptake. Those from mesenchymal stem cells appear to be intrinsically therapeutic,
while those from cancer cells promote tumor progression. Therapeutic proteins can
be loaded into vesicles by overexpression in the donor cell, with oligomerization
and membrane sequences increasing their loading. Examples of protein delivery for
therapeutic benefit in pre-clinical models include delivery of: catalase for
Parkinson's disease to reduce oxidative stress and thus help neurons to survive;
prodrug activating enzymes which can convert a prodrug which crosses the
blood-brain barrier into a toxic chemotherapeutic drug for schwannomas and
gliomas; and the apoptosis-inducing enzyme, caspase-1 under a Schwann cell
specific promoter for schwannoma. This therapeutic delivery strategy is novel and
being explored for a number of diseases.
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