Other groups previously have worked on developing antibodies for cocaine treatment. A drawback to such antibodies and other protein-based therapeutics is that they act on the cocaine peripherally—outside the central nervous system.

	ANTIBODY FERRY Single-chain antibody (pink and blue) that binds cocaine is displayed on the pVIII coat of the virus (green). Courtesy of Kim Janda

Chemistry professor Kim D. Janda and his team modified the viruses so that they display the anticocaine antibody on the viruses’ major coat protein (protein-8 or pVIII), which is abundant enough to display many copies—possibly thousands—of the antibody on each virus.

The researchers gave rats the viruses by intranasal injection twice a day for three days. They then injected the animals with systemic doses of cocaine for four consecutive days and monitored the rats’ behavior. The virus levels dropped off after a couple of weeks, so the vaccine would need to be administered frequently.

One behavioral test uses cages crossed by infrared beams. Because cocaine is a stimulant, a rat on cocaine “will move around more and break the beams of light,” Janda says. The second test involves observing “sniffing and rearing” behavior, in which a rat will stop and lift itself up on its hind legs. The rats that received the viruses demonstrated fewer of the usual responses to cocaine than the control rats.

The antibody-decorated viruses won’t be ready for use in humans for quite some time. “I’m not going to lie to you,” Janda says. “We’re not going to be in the clinic in the next year or two.”
In the future, Janda expects that bacteriophages could be used to deliver other types of proteins as well. “We’d like to move forward and see what happens if we display an enzyme, because an enzyme could have better efficiency.” Enzymes could be used to treat conditions other than drug addiction.

John R. Cashman, director of the Human BioMolecular Research Institute, San Diego, says: “What is particularly striking is the authors’ merging of three exciting fields of research—nasal drug delivery, gene/protein delivery, and phage display—to accomplish their goals. The interdisciplinary approach is a real tour de force and shows that even relatively large particles can be delivered to the brain.”