Preclinical Safety Validation of a Stabilized Viral Vector Direct Injection Approach to the Cervical Spinal Cord

• Type of Material: Article
• Authors: Thais Federici, Emory University; Jonathan Riley, Case Western Reserve University; John Park, Cleveland Clinic; Mark Bain, Cleveland Clinic; Nicholas Boulis, Emory University
• Language: English
• Date: 2009-04-01
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2009 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1111/j.1752-8062.2008.00084.x
• Title of Journal or Parent Work: CTS-CLINICAL AND TRANSLATIONAL SCIENCE
• Volume: 2
• Issue: 2
• Start Page: 165
• End Page: 167
• Grant/Funding Information: This research was supported by the ALS Association.
• Keywords: SURVIVAL; targeted delivery; CELLS; Life Sciences & Biomedicine; MODEL; adeno-associated viral vector; Science & Technology; DELIVERY; pig; gene therapy; cervical spinal cord; Research & Experimental Medicine; PERFUSION; Medicine, Research & Experimental; TRANSPLANTATION; MICE; BRAIN-STEM
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Genetics

Abstract

The current lack of a validated intraspinal delivery approach precludes translation of promising cell or viral-based therapeutics for treatment of varied spinal cord afflictions. We have developed a stabilized cervical microinjection platform with the intent of precise delivery to intraspinal sites of interest. Nine 30-40 kg female swine underwent coordinate-based microinjection AAV2-GFP at three injected volumes (10, 25, and 50 μL (n = 3/group)) and matched infusion rates (1.0, 2.5, and 5.0 μL/min) over a period (t = 10 minutes). Preliminary validation is provided by behavioral and targeting data demonstrating safe delivery of a viral vector carrying a fluorescent reporter gene to the cervical spinal cord ventral horn.