A Safe and Reliable Technique for CNS Delivery of AAV Vectors in the Cisterna Magna

UMMS Affiliation

Horae Gene Therapy Center; Department of Radiology; Department of Neurological Surgery; Department of Neurology; Department of Pediatrics; Department of Microbiology and Physiological Systems; Department of Medicine

Publication Date


Document Type



Analytical, Diagnostic and Therapeutic Techniques and Equipment | Genetic Phenomena | Genetics and Genomics | Molecular Biology | Nervous System | Radiology | Viruses


Global gene delivery to the CNS has therapeutic importance for the treatment of neurological disorders that affect the entire CNS. Due to direct contact with the CNS, cerebrospinal fluid (CSF) is an attractive route for CNS gene delivery. A safe and effective route to achieve global gene distribution in the CNS is needed, and administration of genes through the cisterna magna (CM) via a suboccipital puncture results in broad distribution in the brain and spinal cord. However, translation of this technique to clinical practice is challenging due to the risk of serious and potentially fatal complications in patients. Herein, we report development of a gene therapy delivery method to the CM through adaptation of an intravascular microcatheter, which can be safely navigated intrathecally under fluoroscopic guidance. We examined the safety, reproducibility, and distribution/transduction of this method in sheep using a self-complementary adeno-associated virus 9 (scAAV9)-GFP vector. This technique was used to treat two Tay-Sachs disease patients (30 months old and 7 months old) with AAV gene therapy. No adverse effects were observed during infusion or post-treatment. This delivery technique is a safe and minimally invasive alternative to direct infusion into the CM, achieving broad distribution of AAV gene transfer to the CNS.


AAV clinical trial, AAV gene therapy, AAV9, CSF delivery, Tay-Sachs, cisterna magna, intravascular microcatheter, large animal, lysosomal storage disease

DOI of Published Version



Mol Ther. 2019 Nov 16. pii: S1525-0016(19)30508-8. doi: 10.1016/j.ymthe.2019.11.012. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

Molecular therapy : the journal of the American Society of Gene Therapy


Full author list omitted for brevity. For the full list of authors, see article.

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