The blood-brain barrier has been a major hurdle to transporting gene-silencing or RNA-interference (RNAi) drugs into the brain to treat illnesses such as Alzheimer's disease and other neurological disorders. Yet researchers at the University of Oxford might have found one potential way to penetrate this barrier and deliver RNAi treatments into brain cells.
In a mouse study, the group showed that modified versions of exosomes, which are naturally occurring carriers of RNA molecules and other proteins among cells, were able to deliver small interfering RNAs (siRNA) to specific sites in the brain and turn off an Alzheimer's disease gene target called BACE1. The study was published online on March 20 in Nature Biotechnology.
"This is innovative research, but at such an early stage it's still a long way from becoming a treatment for patients," Simon Ridley, head of research at Alzheimer's Research UK, told BBC News. "Designing drugs that cross the blood brain barrier is a key goal of research that holds the promise of improving the effectiveness of Alzheimer's treatments in the future."
To reduce immune reactions to the tiny exosomes, the Oxford scientists used dendritic cells from mice to produce them. The exosomes were also loaded with siRNA and engineered to express a protein that was then fused to a rabies virus peptide. The rabies virus peptide enabled the compound to home in on specific targets such as neurons in the brain to deliver the siRNA. For mice injected with the compound, the group reported a 60-percent drop in activity of the intended Alzheimer's gene.