Researchers from the University of Oxford used exosomes - small cellular transporters - to deliver a therapeutic agent to the brains of mice. It is hoped the discovery, published in Nature Biotechnology, will lead to the development of more effective drugs that act across the blood-brain barrier.
What did researchers find?
A new type of gene therapy uses short interfering RNAs (siRNAs) to modify gene expression associated with particular pathologies. But recent advances have stalled due to difficulties in targeting specific tissues or cell types and avoiding non-specific effects on organs, such as the liver.
Evading the natural immune response to delivery methods is a further barrier to progress.
Researchers led by Matthew Wood attempted to overcome these challenges by using exosomes - natural cellular transporters of proteins and RNA molecules.
The team grew immune cells from harvested mouse bone marrow to produce a pool of immunologically inert exosomes. These were primed with peptides called rabies viral glycoproteins (RVG) that allow exosomes to be transported to brain tissue.
Researchers loaded the exosomes with siRNAs designed to 'knock out', or reduce expression of, the gene BACE1, a therapeutic target in Alzheimer's disease.
Researchers found that when these were injected into mice, the siRNA entered brain tissue as hoped. They witnessed 60 per cent reduced expression of the BACE1 gene and 62 per cent lower production of the BACE1 protein.
Are the findings significant?
The discovery means that drugs acting across the blood brain barrier may be possible for the first time.
Researchers concluded: 'RVG exosomes are especially capable of delivering siRNA specifically and safely after systemic administration and therefore represent a promising vehicle for gene therapies targeting chronic neurodegenerative disorders.'
They added: 'Moreover, lack of non-specific knock-down in the liver and other organs marks a major improvement over most current siRNA delivery strategies.'
The Alzheimer's Society described the findings as 'exciting'. Susanne Sorensen, head of research at the Alzheimer's Society, said: 'If this delivery method proves safe in humans, then we may see more effective drugs being made available for people with Alzheimer's in the future.'
She said that more research was needed to prove effectiveness in people with Alzheimer's, but warned this work was 'desperately underfunded'.
'To make the breakthroughs we need, we must invest now,' she said.