New Breakthrough for Brain and Spinal Cord Gene Delivery Systems

NIH-Funded Scientists Develop Breakthrough Gene Delivery System for Brain and Spinal Cord

May 22, 2025

In a significant advancement for neurological therapeutics, researchers funded by the National Institutes of Health (NIH) have engineered a novel gene delivery system capable of efficiently crossing the blood-brain barrier (BBB) to target cells within the brain and spinal cord. This innovation holds promise for treating a range of neurodegenerative and genetic disorders that have long eluded effective therapies.

Overcoming the Blood-Brain Barrier

The BBB serves as a protective shield, preventing harmful substances from entering the central nervous system (CNS). However, this defense mechanism also poses a challenge for delivering therapeutic agents to the brain. Traditional adeno-associated viruses (AAVs) used for gene therapy often struggle to penetrate this barrier, limiting their efficacy in treating CNS disorders.

Addressing this issue, a team led by Dr. Benjamin Deverman at the Broad Institute of MIT and Harvard developed an engineered AAV, named BI-hTFR1, designed to bind to the human transferrin receptor (TfR1). TfR1 is abundantly expressed on the BBB and facilitates the transport of iron into the brain. By leveraging this receptor, BI-hTFR1 effectively ferries genetic material across the BBB and into the CNS.

Promising Preclinical Results

In preclinical studies involving human cell models and genetically modified mice expressing human TfR1, BI-hTFR1 demonstrated remarkable efficiency. The engineered AAV achieved widespread distribution throughout the brain and spinal cord, delivering therapeutic genes to critical cell types. Notably, it reached up to 92% of astrocytes and 71% of neurons, surpassing the performance of existing AAVs used in CNS therapies .

Further experiments showcased BI-hTFR1’s capability to deliver the GBA1 gene, mutations of which are linked to Gaucher disease and Parkinson’s disease. The new AAV delivered 30 times more copies of GBA1 compared to traditional vectors, indicating its potential for treating various neurodegenerative conditions .

Broader Implications for Neurological Disorders

The success of BI-hTFR1 opens avenues for treating a spectrum of CNS disorders, including Huntington’s disease, Rett syndrome, and certain forms of amyotrophic lateral sclerosis (ALS). By enabling efficient gene delivery to the brain and spinal cord, this technology could revolutionize the approach to managing diseases previously deemed untreatable .

Future Directions and Clinical Translation

While the preclinical results are promising, further research is necessary to assess the safety, efficacy, and scalability of BI-hTFR1 in human subjects. The research team is exploring strategies to minimize off-target effects and immune responses, as well as to optimize manufacturing processes for clinical applications .

This breakthrough represents a significant stride toward effective gene therapies for neurological diseases, offering hope to patients and families affected by these challenging conditions.

Read more here- https://www.nih.gov/news-events/news-releases/scientists-design-gene-delivery-systems-cells-brain-spinal-cord