Transgenic Biosensors for Organophosphorous Poisoning and the Protective Efficacy of Defense Agents Toward an Engineered Cholinesterase Decoy
Abstract
We have successfully developed the transient transgenic Xenopus tadpole as a useful in vitro model in which to test potential defense agents (Ben Aziz-Aloya et al., 1993). We are now directing attention to development of the defense agent itself. Our goal has been to develop an antidote for organophosphorus chemical agents (OPs), based on an engineered human butyrylcholinesterase (hBuChE). Among the reasons for basing the development on hBuChE are: (1) It already offers limited protection, reacting with OPs and sparing acetylcholinesterase (hAChE) of the CNS and neuromuscular junctions. (2) As a serum enzyme, it will protect against systemic effects of OPs. (3) Variants are likely to be non-immunogenic, as there are no known autoimmune complications involving hBuChE, and the Changes we wish to introduce in the enzyme are not on exposed surfaces. (4) Natural variations of the level of hBuChE activity are well-tolerated (Neville et al., 1992). How will we recognize the ideal variant when we meet it? Our operational requirements for an improved hBuChE are that it: (1) be more sensitive to low levels of OPs, (2) react faster with OPs, (3) be reactivated faster by 2-PAN, and (4) react with a broad range of OPs.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008861
Entities
People
- Hermona Soreq
Organizations
- Hebrew University of Jerusalem