WESTPORT, Jun 07 (Reuters Health) - An antibody-based system shows promise for intracellular delivery of therapeutic proteins. In a series of experiments, Dr. Richard H. Weisbart of the Veterans Affairs Medical Center in Sepulveda, California, and associates have demonstrated that catalase can be transfected into rat cortical neurons, protecting them from oxidative damage.
As reported in the June 1st issue of the Journal of Immunology, the researchers used a previously described monoclonal anti-dsDNA antibody (mAb 3E10) that can penetrate living cells and localize to the nucleus without causing damage. Catalase was covalently linked to mAb 3E10, then incubated with primary rat cortical neurons.
The experiments included "an in vitro model for neuronal cell death in neurodegenerative diseases and stroke...in which primary cortical neurons undergo oxidative-induced injury after exposure to hydrogen peroxide."
The antibody mAb 3E10 alone incubated with the neurons afforded them no protection, and catalase alone provided only slight protection when hydrogen peroxide was introduced into the system.
Incubation of neurons with 40 micrograms/mL mAb 3E10-catalase increased the viability of neurons in the presence of hydrogen peroxide to between 60% and 70%. The neuronal protection by the antibody-catalase conjugate was dose dependent. Thus, the researchers conclude that "the catalase transfected into the neurons...retained biological activity."
"Our studies in vitro support the feasibility of developing an antibody-based delivery system to protect normal neurons from oxidative-induced injury," the investigators propose. "Further studies are needed to address the critical issues related to targeting, transport, and protection of neurons in vivo."
J Immunol 2000;164:6020-6026.