? The goal of this research is to develop anti-drug single chain antibodies (scFv) as potential medications for treating drug abuse. These scFv will be derived from the variable region domains of currently available anti- (+)methamphetamine monoclonal antibodies (mAb). However, they will be reengineered to possess immunological, pharmacokinetic, and affinity advantages over the parent mAb. In the first specific aim, the scFv will be recombinantly engineered by connecting the heavy and light chain variable regions of the prototype mAb with a polypeptide linker to create a single gene product. This product will be produced in bacterial systems, which could lead to less expensive protein medications. In the second aim, in vitrc evolution techniques will then be used to generate scFv with new sequences that are then selected for improved affinity and specificity. In a third aim, chemical modifications of scFv with poly(ethylene glycol) will be used to develop medications with improved pharmacokinetic properties. It is envisioned that an engineered antibody fragment with customized affinity and pharmacokinetic properties will be an important innovation for the treatment of methamphetamine abuse. ? ? ? ?
