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AAV vectors accumulate in the pineal gland after injections into the brain or spinal cord
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 t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560646/ https://www.ncbi.nlm.nih.gov/pubmed/34761054 http://dx.doi.org/10.1016/j.omtm.2021.09.016 |
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author | Steward, Oswald Coulibaly, Aminata P. Metcalfe, Mariajose Dam, Jamie M. Yee, Kelly M. |
author_facet | Steward, Oswald Coulibaly, Aminata P. Metcalfe, Mariajose Dam, Jamie M. Yee, Kelly M. |
author_sort | Steward, Oswald |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8560646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-85606462021-11-09 AAV vectors accumulate in the pineal gland after injections into the brain or spinal cord Steward, Oswald Coulibaly, Aminata P. Metcalfe, Mariajose Dam, Jamie M. Yee, Kelly M. Mol Ther Methods Clin Dev Original Article 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. American Society of Gene & Cell Therapy 2021-10-05 /pmc/articles/PMC8560646/ /pubmed/34761054 http://dx.doi.org/10.1016/j.omtm.2021.09.016 Text en © 2021 The Authors. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Article Steward, Oswald Coulibaly, Aminata P. Metcalfe, Mariajose Dam, Jamie M. Yee, Kelly M. AAV vectors accumulate in the pineal gland after injections into the brain or spinal cord |
title | AAV vectors accumulate in the pineal gland after injections into the brain or spinal cord |
title_full | AAV vectors accumulate in the pineal gland after injections into the brain or spinal cord |
title_fullStr | AAV vectors accumulate in the pineal gland after injections into the brain or spinal cord |
title_full_unstemmed | AAV vectors accumulate in the pineal gland after injections into the brain or spinal cord |
title_short | AAV vectors accumulate in the pineal gland after injections into the brain or spinal cord |
title_sort | aav vectors accumulate in the pineal gland after injections into the brain or spinal cord |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560646/ https://www.ncbi.nlm.nih.gov/pubmed/34761054 http://dx.doi.org/10.1016/j.omtm.2021.09.016 |
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