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A Safe and Reliable Technique for CNS Delivery of AAV Vectors in the Cisterna Magna.
Taghian, Toloo; Marosfoi, Miklos G; Puri, Ajit S; Cataltepe, Oguz I; King, Robert M; Diffie, Elise B; Maguire, Anne S; Martin, Douglas R; Fernau, Deborah; Batista, Ana Rita; Kuchel, Tim; Christou, Chris; Perumal, Raj; Chandra, Sundeep; Gamlin, Paul D; Bertrand, Stephanie G; Flotte, Terence R; McKenna-Yasek, Diane; Tai, Phillip W L; Aronin, Neil; Gounis, Matthew J; Sena-Esteves, Miguel; Gray-Edwards, Heather L.
Afiliación
  • Taghian T; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Marosfoi MG; Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Puri AS; Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Neurological Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Cataltepe OI; Department of Neurological Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • King RM; Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Diffie EB; Scott-Ritchey Research Center, Auburn University, Auburn, AL 36849, USA.
  • Maguire AS; Scott-Ritchey Research Center, Auburn University, Auburn, AL 36849, USA.
  • Martin DR; Scott-Ritchey Research Center, Auburn University, Auburn, AL 36849, USA; Department of Anatomy, Physiology and Pharmacology, Auburn University, AL 36849, USA.
  • Fernau D; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Batista AR; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Kuchel T; South Australian Health and Medical Research Institute, Gillies Plains, SA 5086, Australia.
  • Christou C; South Australian Health and Medical Research Institute, Gillies Plains, SA 5086, Australia.
  • Perumal R; South Australian Health and Medical Research Institute, Gillies Plains, SA 5086, Australia.
  • Chandra S; BioMarin Pharmaceutical Inc., San Rafael, CA 94901, USA.
  • Gamlin PD; Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Bertrand SG; Department of Environmental Population Health, Cummings Veterinary School at Tufts University, Grafton, MA 01536, USA.
  • Flotte TR; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • McKenna-Yasek D; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Tai PWL; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Aronin N; Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Gounis MJ; Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Sena-Esteves M; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Gray-Edwards HL; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: heather.grayedwards@umassmed.edu.
Mol Ther ; 28(2): 411-421, 2020 02 05.
Article en En | MEDLINE | ID: mdl-31813800
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción Genética / Expresión Génica / Cisterna Magna / Técnicas de Transferencia de Gen / Dependovirus / Vectores Genéticos Tipo de estudio: Guideline Límite: Animals / Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción Genética / Expresión Génica / Cisterna Magna / Técnicas de Transferencia de Gen / Dependovirus / Vectores Genéticos Tipo de estudio: Guideline Límite: Animals / Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos