ArticleMolecular therapy. Methods & clinical development2021
AAV vectors accumulate in the pineal gland after injections into the brain or spinal cord.
Article in Molecular therapy. Methods & clinical development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Proceedings of the 2024 Division of Translational Toxicology Satellite Symposium.Toxicologic pathology · 2024Article
- Harnessing rAAV-retro for gene manipulations in multiple pathways that are interrupted after spinal cord injury.Experimental neurology · 2022Article
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5 authors.
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Abstract
AAV vectors are being used extensively for gene-modifying therapies for neurological disorders. Here, we report the surprising discovery that injections of different AAVs into the brain, spinal cord, or cerebrospinal fluid (CSF) lead to robust transduction of cells in the pineal gland. We document transduction of cells in the pineal gland following focal injections of AAV2/9-shPTEN-zsGreen into the sensorimotor or hippocampus of rats and injections of AAV2/Cre into the spinal cord of transgenic mice with a stop-flox tdT reporter. Pineal transduction was evident even when AAV2/Cre injections were made into the lumbar spinal cord many millimeters distant from the pineal gland. Immunostaining with antibodies for cell types in the pineal gland revealed that pinealocytes were transduced. Pineal transduction was also observed with intracerebroventricular (i.c.v.) injections of AAV2/9-shPTEN-zsGreen, suggesting that pineal transduction following focal injections of AAV into CNS parenchyma may be caused by diffusion of the vector from the injection sites into the CSF and then accumulation in the pineal gland. Together, these findings suggest the need for vigilance for functional consequences and possible adverse effects of off-target accumulation of therapeutic AAVs in the pineal gland and AAV-driven expression of therapeutic cargos in pinealocytes.
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