ArticlePloS one2012
In vivo gene knockdown in rat dorsal root ganglia mediated by self-complementary adeno-associated virus serotype 5 following intrathecal delivery.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- OPRM1/MRGPRX1 heterodimers drive opioid-induced itch through a peripheral mechanism.Journal of biomedical science · 2026Article
- Recent Advances in In Vivo Somatic Cell Gene Modification in Newborn Pups.International journal of molecular sciences · 2023Review
- Comparison of the efficiencies of intrathecal and intraganglionic injections in mouse dorsal root ganglion.Turkish journal of medical sciences · 2023Article
- Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Optimization of AAV vectors to target persistent viral reservoirs.Virology journal · 2021Review
- Long-lasting analgesia via targeted in situ repression of NaScience translational medicine · 2021Article
- AAV-Mediated Combination Gene Therapy for Neuropathic Pain: GAD65, GDNF, and IL-10.Molecular therapy. Methods & clinical development · 2020Article
- On the development of optical peripheral nerve interfaces.Neural regeneration research · 2019Review
- Adeno-associated virus 2/9 delivery of Cre recombinase in mouse primary afferents.Scientific reports · 2018Article
- Adeno-associated virus serotype rh10 is a useful gene transfer vector for sensory nerves that innervate bone in immunodeficient mice.Scientific reports · 2017Article
- Subpial Adeno-associated Virus 9 (AAV9) Vector Delivery in Adult Mice.Journal of visualized experiments : JoVE · 2017Article
- In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia.Scientific reports · 2017Article
- Current and Future Issues in the Development of Spinal Agents for the Management of Pain.Current neuropharmacology · 2017Review
- In vivo disruption of latent HSV by designer endonuclease therapy.JCI insight · 2016Article
- Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs.Molecular therapy. Methods & clinical development · 2016Article
- Virus-Mediated Knockdown of Nav1.3 in Dorsal Root Ganglia of STZ-Induced Diabetic Rats Alleviates Tactile Allodynia.Molecular medicine (Cambridge, Mass.) · 2015Article
- A compact dual promoter adeno-associated viral vector for efficient delivery of two genes to dorsal root ganglion neurons.Gene therapy · 2014Article
- Transgenic models of Alzheimer's disease: better utilization of existing models through viral transgenesis.Biochimica et biophysica acta · 2013Review
- Intraperitoneal administration of AAV9-shRNA inhibits target gene expression in the dorsal root ganglia of neonatal mice.Molecular pain · 2013Article
- Gene therapy for misfolding protein diseases of the central nervous system.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2013Review
Corrections and comments
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Authors and funding
9 authors.
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Abstract
We report here in adult rat viral vector mediate-gene knockdown in the primary sensory neurons and the associated cellular and behavior consequences. Self-complementary adeno-associated virus serotype 5 (AAV5) was constructed to express green fluorescent protein (GFP) and a small interfering RNA (siRNA) targeting mammalian target of rapamycin (mTOR). The AAV vectors were injected via an intrathecal catheter. We observed profound GFP expression in lumbar DRG neurons beginning at 2-week post-injection. Of those neurons, over 85% were large to medium-diameter and co-labeled with NF200, a marker for myelinated fibers. Western blotting of mTOR revealed an 80% reduction in the lumbar DRGs (L4-L6) of rats treated with the active siRNA vectors compared to the control siRNA vector. Gene knockdown became apparent as early as 7-day post-injection and lasted for at least 5 weeks. Importantly, mTOR knockdown occurred in large (NF200) and small-diameter neurons (nociceptors). The viral administration induced an increase of Iba1 immunoreactivity in the DRGs, which was likely attributed to the expression of GFP but not siRNA. Rats with mTOR knockdown in DRG neurons showed normal general behavior and unaltered responses to noxious stimuli. In conclusion, intrathecal AAV5 is a highly efficient vehicle to deliver siRNA and generate gene knockdown in DRG neurons. This will be valuable for both basic research and clinic intervention of diseases involving primary sensory neurons.
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