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Extracell Vesicles Circ Nucleic Acids 2020;1:20-56 I http://dx.doi.org/10.20517/evcna.2020.10 Page 51

Abstracts:
Extracellular vesicles have advantageous properties for drug delivery applications, including non-
immunogenicity and homing capacity. Important parameters for efficient drug delivery to the brain using
(natural) nanocarriers are efficient crossing of the blood-brain barrier (BBB) and spatiotemporal control of
cargo release.

Here we show that EVs derived from neural stem cells (NSCs) are taken up by brain microvascular
[1]
endothelial cells following binding to heparan sulfate proteoglycans, and efficiently cross the BBB .

In addition, we developed an analytical methodology, combining state-of-the-art molecular tools and
correlative light and electron microscopy to demonstrate that EV cargo release occurs from endosomes/
[2]
lysosomes .
Finally, we have explored the potential of neural stem cell derived EVs enriched with DNAJB6 as a
therapeutic intervention for Huntington’s disease (HD). HD is a neurodegenerative disorder characterized
by aggregation of the huntingtin (HTT) protein containing expanded polyglutamine (polyQ) tracts.
DNAJB6, a DNAJ chaperone, has been reported to efficiently inhibit polyQ aggregation in vitro in cell
[3]
models, and in vivo in HD animal models . Administration of DNAJB6-containing EVs to cells expressing
expanded polyQ tracts suppressed HTT aggregation. Furthermore, intrathecal injection of DNAJB6-
enriched EVs into R6/2 transgenic HD mice significantly reduced mutant HTT aggregation in the brain .
[4]
Taken together, our data suggest that EV-mediated molecular chaperone delivery may be an effective way
to reduce polyQ aggregation and potentially treat polyQ diseases, including HD.

REFERENCES
1. Joshi BS, Zuhorn IS. Heparan sulfate proteoglycan-mediated dynamin-dependent transport of neural stem cell exosomes in an in vitro
blood-brain barrier model. Eur J Neurosci. 2020; doi: 10.1111/ejn.14974.
2. Joshi BS, de Beer MA, Giepmans BNG, et al. Endocytosis of Extracellular Vesicles and Release of Their Cargo from Endosomes. ACS
Nano. 2020;14:4444-55.
3. Kakkar V, Månsson C, de Mattos EP, et al. The S/T-Rich Motif in the DNAJB6 Chaperone Delays Polyglutamine Aggregation and the
Onset of Disease in a Mouse Model. Mol Cell. 2016;62:272-83.
4. Joshi BS, Youssef SA, Bron R, et al. DNAJB6b-enriched exosomes decrease polyglutamine aggregation in in vitro and in vivo models of
Huntington’s disease. (submitted)

42. The uptake, trafficking, and biodistribution of Bacteroides thetaiotaomicron (Bt) generated
outer membrane vesicles

Authors: Simon Carding
E-mail: Simon.Carding@quadram.ac.uk
Affiliations:
Gut Microbes and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich United Kingdom.
Norwich Medical School, University East Anglia, Norwich, United Kingdom.

Abstracts: The human gastrointestinal tract is home to hundreds of trillions of microorganisms (the
microbiome) that perform a vital role in food digestion and providing essential nutrients and vitamins.
They also play an important role in metabolizing medicines and drugs, and in resisting infection by
pathogens. Gut microbes are however susceptible to change with alterations in their makeup and activity
occurring as a result of exposure to various environmental factors such as diet, drugs, pathogens and
behaviour. Such changes have been associated with more than 90% of human diseases affecting the gut,