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  4. Harnessing rAAV-retro for gene manipulations in multiple pathways that are interrupted after spinal cord injury

Harnessing rAAV-retro for gene manipulations in multiple pathways that are interrupted after spinal cord injury

Exp Neurol, 2022 · DOI: 10.1016/j.expneurol.2021.113965 · Published: April 1, 2022

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

This research explores using a special virus (rAAV2-retro) to deliver gene-modifying instructions to nerve cells affected by spinal cord injury. The virus travels backward along nerve pathways to reach the cells' origin. Unlike previous methods that targeted one nerve pathway at a time, this virus can reach multiple pathways simultaneously, offering a more comprehensive approach to treating spinal cord injuries. The researchers successfully used this virus to deliver instructions that modify a specific gene (PTEN) in multiple nerve cell populations, demonstrating the potential of this method for gene-based therapies after spinal cord injury.

Study Duration
Not specified
Participants
Mice and Rats
Evidence Level
Not specified

Key Findings

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    rAAV-retro can simultaneously transduce large numbers of neurons of origin of multiple spinal pathways with single injections into the spinal cord.
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    rAAV-retro expressing shRNA against PTEN along with a GFP reporter (rAAV-retro-shPTEN/GFP) to effectively knock down PTEN in multiple populations of neurons, which can be used in any species.
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    A single intra-spinal injection of rAAV-retro can deliver cargos to thousands of the cells of origin of multiple spinal pathways.

Research Summary

This paper explores the potential of rAAV2-retro to deliver gene modifying cargoes to the cells of origin of multiple pathways that are interrupted by spinal cord injury (SCI), summarizing data from previous studies and new data from additional experiments. Our results confirm and extend previous studies indicating selective transduction of neurons that terminate at the level of the injection with minimal retrograde transduction of axons in transit to lower levels. our results support the potential applications of rAAV-retro for AAV-based gene-modifications for SCI.

Practical Implications

Targeted Gene Delivery

rAAV-retro allows for targeted delivery of gene-modifying cargos to multiple spinal pathways simultaneously, which can enhance regeneration and functional recovery after SCI.

Therapeutic Development

The study demonstrates the feasibility of using rAAV-retro in rats, paving the way for therapeutic development applicable to various species without prior genetic modifications.

Intersectional Genetics

The use of rAAV-retro in combination with intersectional genetics enables selective transduction of defined sets of neurons, facilitating studies of specific pathways and their functions after SCI.

Study Limitations

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