Novel Genome-editing Strategy for Potential Alzheimer’s Disease Therapy

Familial Alzheimer’s disease (FAD) accounts for 3-5% of AD cases. Although it has a clear genetic cause, no effective disease-modifying treatments currently exist. Genome-editing technology has the potential as a therapeutic strategy for FAD, which can eliminate disease-causing genetic mutations before symptoms appear and has “once-and-for-all” long-acting treatment effects. However, several hurdles have prevented its clinical development and application - most notably the lack of an effective, efficient, and non-invasive means to deliver genome-editing agents into the brain. Furthermore, existing genome-editing technologies are unable to generate beneficial outcomes throughout the whole brain. This brain-wide genome-editing technology uses a newly engineered delivery vehicle for genome-editing and achieves efficient brain-wide genome editing through a single non-invasive intravenous administration, representing a promising approach for FAD treatment.

• First time in the world to achieve non-invasive brain-wide genome editing in the adult stage
• Novel therapeutic strategy for familial Alzheimer's disease – novel gene therapy approach to eliminate disease-causing mutations and effectively alleviate the pathological symptoms of Alzheimer's disease throughout the brain in animal model

• “Once-and-for-all” treatment effect: The brain-wide genome-editing technology can directly eliminate genetic mutations causing familial Alzheimer’s disease. It can effectively and efficiently treat familial AD and alleviate disease pathologies for a long time.
• Brain-wide beneficial effects: Current genome-editing strategies for brain disorders are delivered via intraparenchymal injection, which affects limited brain regions with restricted beneficial outcomes. Since AD affects multiple brain regions, it is difficult to achieve widespread and effective therapeutic effects by administering drugs to a small part of the brain. The new technology can cross the blood-brain barrier, achieving efficient genome editing among the whole brain and hence generating beneficial effects throughout the brain.
• Non-invasiveness: The drug is administered through a single non-invasive intravenous injection, instead of the conventional invasive gene therapy delivery approaches, such as intraparenchymal injection and intracerebroventricular injection, which require craniotomy for the injection.

• Major Progress Award for Neuroscience in China (2021)

• A viable strategy for the treatment of familial Alzheimer’s disease and other forms of brain disease that are caused by dominant mutations that affect multiple brain regions