Gene and Protein Therapy for Poisoning by Organophosphorus Agents
Abstract
The goal of this work is to find new protection strategies against the toxicity of nerve agents. A gene therapy protocol capable of delivering human acetylcholinesterase into dividing as well as nondividing cells has been developed, using adeno-associated virus to transfer the gene. Mice treated with this virus expressed human acetylcholinesterase. A transgenic mouse line was established that expresses human Cll7H butyrylcholinesterase in all tissue. The Gll7H butyrylcholinesterase gene was selected for expression in mice because of its special properties. It hydrolyzes nerve agents pesticides, and other organophosphorus esters, and also hydrolyzes the neurotransmitter acetylchoine. When G117H butyrylcholinesterase transgenic mice had only mild signs of toxicity and no lethality. This is the first transgenic mouse successfully engineered for resistance to organophosphate toxicity. It demonstrates that small quantities of human G117H buturulcholinesterase provide protection in a living animal.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA418803
Entities
People
- Oksana Lockridge
Organizations
- University of Nebraska Medical Center