Non-Invasive Method Delivers Genes to the Central Nervous System

December 22, 2008

Investigators at The Research Institute at Nationwide Childrens Hospital have identified a non-invasive method for delivering genes to the central nervous system, a strategy that penetrates the bodys protective blood-brain barrier with unprecedented success.

The blood-brain barrier (BBB) is a protective network of blood vessels and cells that prevents many substances from entering brain tissue and the central nervous system. While the BBB functions as a vital biological shield, it can also serve as a barrier to treating central nervous system disorders.

Previous gene therapy efforts to treat two of the most common motor neuron diseases, spinal muscular atrophy (SMA) and ALS (Lou Gehrigs disease), have either failed to bypass the BBB, or are clinically irrelevant since they require interventions considered too numerous or too complicated.

In this study, which appears in Nature Biotechnology, members of the Center for Gene Therapy at The Research Institute used AAV9, a subtype of the adeno-associated virus, as the vehicle for gene transfer.

Using a single injection, researchers delivered AAV9 and examined its potential to transport genes to the central nervous system in neonatal and adult mouse models.  Results showed AAV9 accessed the central nervous system with unmatched efficiency. 

In the neonatal model, AAV9 preferentially targeted basic nerve cells (neurons).  In adults it more often targeted astrocytes, the largest and most common nerve cells in the central nervous system. These differences suggest there is a developmental period during which viral access to these cell populations becomes restricted. 

The precise mechanism by which AAV9 penetrates the BBB and facilitates gene transfer will require further study.  Still, researchers believe the relatively non-invasive method described in this study could have important implications for gene therapy treatments in SMA and ALS. A suggested therapeutic for SMA is an increased expression of the survival motor neuron gene; this studys single injection method could potentially achieve this outcome. Astrocytes, which were efficiently targeted in both the neonatal and adult models in this study, have been specifically linked to disease progression in ALS. 

Additionally, new techniques stemming from this AAV9 research could target neurons in adults.  Such strategies could provide new treatment options for diseases such as Huntingtons that involve multiple brain regions.

About Nationwide Children's Hospital

Named to the Top 10 Honor Roll on U.S. News & World Report ‘s 2018-19 list of “Best Children’s Hospitals,” Nationwide Children’s Hospital is one of America’s largest not-for-profit freestanding pediatric health care systems providing wellness, preventive, diagnostic, treatment and rehabilitative care for infants, children and adolescents, as well as adult patients with congenital disease. Nationwide Children’s has a staff of more than 13,000 providing state-of-the-art pediatric care during more than 1.4 million patient visits annually. As home to the Department of Pediatrics of The Ohio State University College of Medicine, Nationwide Children’s physicians train the next generation of pediatricians and pediatric specialists. The Research Institute at Nationwide Children’s Hospital is one of the Top 10 National Institutes of Health-funded freestanding pediatric research facilities. More information is available at