title: AAV viral vector delivery to the brain by shape-conforming MR-guided infusions.
abstract: Gene transfer technology offers great promise as a potential therapeutic approach to the brain but has to be viewed as a very complex technology. Success of ongoing clinical gene therapy trials depends on many factors such as selection of the correct genetic and anatomical target in the brain. In addition, selection of the viral vector capable of transfer of therapeutic gene into target cells, along with long-term expression that avoids immunotoxicity has to be established. As with any drug development strategy, delivery of gene therapy has to be consistent and predictable in each study subject. Failed drug and vector delivery will lead to failed clinical trials. In this article, we describe our experience with AAV viral vector delivery system, that allows us to optimize and monitor in real time viral vector administration into affected regions of the brain. In addition to discussing MRI-guided technology for administration of AAV vectors we have developed and now employ in current clinical trials, we also describe ways in which infusion cannula design and stereotactic trajectory may be used to maximize the anatomical coverage by using fluid backflow. This innovative approach enables more precise coverage by fitting the shape of the infusion to the shape of the anatomical target.
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94110, USA. Electronic address: Krystof.Bankiewicz@ucsf.edu.
authors.forename: Krystof S
authors.initials: KS
authors.lastname: Bankiewicz
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94110, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Sudhakar
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94110, USA.
authors.forename: Lluis
authors.initials: L
authors.lastname: Samaranch
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94110, USA.
authors.forename: Waldy
authors.initials: W
authors.lastname: San Sebastian
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94110, USA.
authors.forename: John
authors.initials: J
authors.lastname: Bringas
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94110, USA.
authors.forename: John
authors.initials: J
authors.lastname: Forsayeth
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002986:Clinical Trials as Topic; D000229:Dependovirus / Q000235:genetics*; D004867:Equipment Design; D018014:Gene Transfer Techniques / Q000295:instrumentation; D015316:Genetic Therapy / Q000295:instrumentation / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000628:therapy
keywords: Adeno-associated virus; Axonal transport; Brain delivery; Clinical trial; Gene therapy; MRI; Pre-clinical research; Shape fitting