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A Hybrid Extracellular vesicle/virus Vector System for Gene Therapy Applications

Monday, 24 March 2014 at 16:30

Add to Calendar ▼2014-03-24 16:30:002014-03-24 17:30:00Europe/LondonA Hybrid Extracellular vesicle/virus Vector System for Gene Therapy Applications Circulating Biomarkers 2014 in Boston, Massachusetts, USABoston, Massachusetts, USASELECTBIOenquiries@selectbiosciences.com

Obtaining tissue-restricted transgene expression after intravenous (i.v.) injection of AAV vectors is a challenging task, especially for the brain, as the majority of vector is taken up by the liver. Although some vectors can cross the intact blood-brain barrier, improvements are still needed. Additionally, pre-existing antibodies against AAV can remove vector from the circulation. Other studies have shown that association of virus vectors with nanoparticles, such as microbubbles and cationic liposomes can alter the vector biodistribution to preferred sites.  Another nanoparticle which may offer utility to the field of viral vector gene delivery are extracellular vesicles(EVs).  EVs are small (50-200 nm in diameter) membrane limited structures naturally secreted by many cell types.  We have recently shown that EV-associated AAV vectors (EV-AAV, a.k.a vexosomes) can deliver genes more efficiently on a genome copy per cell basis than AAV vectors alone using cultured cells. In the current study we are using the EV-AAV for targeted gene delivery to the brain after i.v. injection in mice.  To investigate if EV-AAV can be targeted to the brain via over-expression of specific ligands on the EV surface we injected nude mice with EV-AAV9-Fluc or EV-AAV9-Fluc with a brain targeting peptide (RVG) fused to a trasmembrane domain.Enhanced transduction of the brain was observed with the RVG peptide compared to untargeted EV-AAV. The brain:peripheral organ transduction ratio was significantly higher for RVG-EV-AAV compared to standard AAV9.  This work has provides the first evidence for the in vivo use of EV-AAV for gene therapy.