Intraspinal AAV Injections Immediately Rostral to a Thoracic Spinal Cord Injury Site Efficiently Transduces Neurons in Spinal Cord and Brain

Molecular Therapy—Nucleic Acids, 2013 · DOI: 10.1038/mtna.2013.34 · Published: July 23, 2013

Simple Explanation

Researchers explored a new way to deliver gene therapy to the brain and spinal cord after a spinal cord injury. Instead of injecting the therapy directly into the brain, they injected it into the spinal cord near the injury. They used a virus called AAV to carry a gene that makes a fluorescent protein, allowing them to see which cells were affected. The virus was taken up by damaged nerve fibers and transported to nerve cells in the brain. This method successfully delivered the gene to many nerve cells in the brain and spinal cord. They also found that different types of AAV viruses were better at reaching different areas of the brain.

Study Duration

1 Month

Participants

Adult female Sprague–Dawley rats (225–250 g), n=3 per AAV serotype

Evidence Level

Not specified

Key Findings

1
AAV injected into the spinal cord near an injury site can travel to the brain and deliver genes to nerve cells.
2
Different types of AAV viruses have different preferences for which brain areas they reach.
3
AAV5 was the most effective at reaching both the spinal cord and the brain.

Research Summary

The study demonstrates that AAV can be retrogradely transported by axons severed by SCI to transduce supraspinal neurons. Intraspinal injection of AAV near the injury site resulted in transduction of neurons within the spinal cord and multiple regions within the brainstem. Different AAV serotypes showed disparate regional specificity, with AAV5 transducing the most brain and spinal cord neurons.

Practical Implications

Less Invasive Approach

Offers a less invasive method for delivering gene therapy to multiple brain regions after spinal cord injury compared to direct brain injections.

Combinatorial Strategies

This method can be combined with other strategies to promote axonal regeneration and functional recovery after SCI.

Targeted Gene Delivery

Allows for more specific targeting of descending tracts compared to injecting virus throughout the brainstem.

Study Limitations

1
The study focused on whether AAV was transported at all, not on the impact of injury on transport efficiency.
2
The study used an acute SCI model, and it is unknown if AAV is taken up and retrogradely transported by chronically injured axons.
3
The number of transduced neurons may be underestimated due to analyzing only a fraction of brain sections.

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