Intracisternal vs intraventricular injection of AAV1 result in comparable, widespread transduction of the dog brain.

Autor: Hunter JE; Research Institute of Children's Hospital of Philadelphia, Philadelphia, PA, USA., Vite CH; W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Department Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32608, USA., Molony CM; W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., O'Donnell PA; W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Wolfe JH; Research Institute of Children's Hospital of Philadelphia, Philadelphia, PA, USA. jhwolfe@vet.upenn.edu.; W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. jhwolfe@vet.upenn.edu.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. jhwolfe@vet.upenn.edu.
Jazyk: angličtina
Zdroj: Gene therapy [Gene Ther] 2024 Dec 09. Date of Electronic Publication: 2024 Dec 09.
DOI: 10.1038/s41434-024-00510-9
Abstrakt: Widespread distribution of transduced brain cells following delivery of AAV vectors into the cerebrospinal fluid (CSF) of the cisterna magna (CM) has been demonstrated in large animal brains. In humans, intraventricular injection is preferred to intracisternal injection for CSF delivery due to the risk of brain stem injury. One study in the dog reported adverse reactions to AAV vectors expressing GFP injected into the lateral ventricle but not when injected into the CM. In contrast, AAV expressing mammalian genes in diseased animals have not triggered adverse responses since many genetic diseases also have compromised immune systems. Differences in circulation of CSF from each site could potentially affect vector spread within the brain, but a direct comparison has not been made using both a mammalian gene and immunologically normal animals. In this study we evaluated the dopamine-2-receptor (D2R) variant D2R80A, which is inactivated for intracellular signaling and has been used as a reporter gene in large animal brains. No adverse reactions to the D2R80A gene were observed from either injection route in normal dogs and both routes resulted in comparable distribution of D2R80A within the brain.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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