Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery
Multiple studies have examined the transduction characteristics of different AAV serotypes in the mouse brain, where they can exhibit significantly different patterns of transduction. The pattern of transduction also varies with the route of administration. Much less information exists for the trans...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-09-01
|
| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050122000997 |
| _version_ | 1811215953021632512 |
|---|---|
| author | Jacqueline E. Hunter Caitlyn M. Molony Jessica H. Bagel Patricia A. O’Donnell Stephen G. Kaler John H. Wolfe |
| author_facet | Jacqueline E. Hunter Caitlyn M. Molony Jessica H. Bagel Patricia A. O’Donnell Stephen G. Kaler John H. Wolfe |
| author_sort | Jacqueline E. Hunter |
| collection | DOAJ |
| description | Multiple studies have examined the transduction characteristics of different AAV serotypes in the mouse brain, where they can exhibit significantly different patterns of transduction. The pattern of transduction also varies with the route of administration. Much less information exists for the transduction characteristics in large-brained animals. Large animal models have brains that are closer in size and organization to the human brain, such as being gyrencephalic compared to the lissencephalic rodent brains, pathway organization, and certain electrophysiologic properties. Large animal models are used as translational intermediates to develop gene therapies to treat human diseases. Various AAV serotypes and routes of delivery have been used to study the correction of pathology in the brain in lysosomal storage diseases. In this study, we evaluated the ability of selected AAV serotypes to transduce cells in the cat brain when delivered into the cerebrospinal fluid via the cisterna magna. We previously showed that AAV1 transduced significantly greater numbers of cells than AAV9 in the cat brain by this route. In the present study, we evaluated serotypes closely related to AAVs 1 and 9 (AAVs 6, AS, hu32) that may mediate more extensive transduction, as well as AAVs 4 and 5, which primarily transduce choroid plexus epithelial (CPE) and ependymal lining cells in the rodent brain. The related serotypes tended to have similar patterns of transduction but were divergent in some specific brain structures. |
| first_indexed | 2024-04-12T06:32:05Z |
| format | Article |
| id | doaj.art-0a1656607a9844baa60b21f7aa32d924 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-04-12T06:32:05Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-0a1656607a9844baa60b21f7aa32d9242022-12-22T03:43:58ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012022-09-0126384393Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal deliveryJacqueline E. Hunter0Caitlyn M. Molony1Jessica H. Bagel2Patricia A. O’Donnell3Stephen G. Kaler4John H. Wolfe5Research Institute of Children’s Hospital of Philadelphia, 502-G Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USAW.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAW.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAW.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USASection on Translational Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USAResearch Institute of Children’s Hospital of Philadelphia, 502-G Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA; W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding author John H. Wolfe, Children’s Hospital of Philadelphia, 502-G Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4399, USA.Multiple studies have examined the transduction characteristics of different AAV serotypes in the mouse brain, where they can exhibit significantly different patterns of transduction. The pattern of transduction also varies with the route of administration. Much less information exists for the transduction characteristics in large-brained animals. Large animal models have brains that are closer in size and organization to the human brain, such as being gyrencephalic compared to the lissencephalic rodent brains, pathway organization, and certain electrophysiologic properties. Large animal models are used as translational intermediates to develop gene therapies to treat human diseases. Various AAV serotypes and routes of delivery have been used to study the correction of pathology in the brain in lysosomal storage diseases. In this study, we evaluated the ability of selected AAV serotypes to transduce cells in the cat brain when delivered into the cerebrospinal fluid via the cisterna magna. We previously showed that AAV1 transduced significantly greater numbers of cells than AAV9 in the cat brain by this route. In the present study, we evaluated serotypes closely related to AAVs 1 and 9 (AAVs 6, AS, hu32) that may mediate more extensive transduction, as well as AAVs 4 and 5, which primarily transduce choroid plexus epithelial (CPE) and ependymal lining cells in the rodent brain. The related serotypes tended to have similar patterns of transduction but were divergent in some specific brain structures.http://www.sciencedirect.com/science/article/pii/S2329050122000997large animal braingyrencephalicAAVserotypesintrathecalcisterna magna |
| spellingShingle | Jacqueline E. Hunter Caitlyn M. Molony Jessica H. Bagel Patricia A. O’Donnell Stephen G. Kaler John H. Wolfe Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery Molecular Therapy: Methods & Clinical Development large animal brain gyrencephalic AAV serotypes intrathecal cisterna magna |
| title | Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery |
| title_full | Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery |
| title_fullStr | Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery |
| title_full_unstemmed | Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery |
| title_short | Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery |
| title_sort | transduction characteristics of alternative adeno associated virus serotypes in the cat brain by intracisternal delivery |
| topic | large animal brain gyrencephalic AAV serotypes intrathecal cisterna magna |
| url | http://www.sciencedirect.com/science/article/pii/S2329050122000997 |
| work_keys_str_mv | AT jacquelineehunter transductioncharacteristicsofalternativeadenoassociatedvirusserotypesinthecatbrainbyintracisternaldelivery AT caitlynmmolony transductioncharacteristicsofalternativeadenoassociatedvirusserotypesinthecatbrainbyintracisternaldelivery AT jessicahbagel transductioncharacteristicsofalternativeadenoassociatedvirusserotypesinthecatbrainbyintracisternaldelivery AT patriciaaodonnell transductioncharacteristicsofalternativeadenoassociatedvirusserotypesinthecatbrainbyintracisternaldelivery AT stephengkaler transductioncharacteristicsofalternativeadenoassociatedvirusserotypesinthecatbrainbyintracisternaldelivery AT johnhwolfe transductioncharacteristicsofalternativeadenoassociatedvirusserotypesinthecatbrainbyintracisternaldelivery |