A chemical component present in the nightshade family of plants is one of the world’s most tenaciously addictive substances. It is the nicotine contained in tobacco and found in high concentrations in cigarettes. Smoking remains a global scourge; in the U.S. it is the leading source of preventable death.
In the universe of addictive drugs, nicotine reigns supreme in terms of the numbers of people affected. In the U.S. alone, cigarette smoking causes some 443,000 fatalities per year – exacting a greater human toll than the human immunodeficiency virus (HIV), illegal drug use, alcohol use, motor vehicle injuries, suicides and murders combined, according to the Center for Disease Control.
While various elements in cigarettes and other tobacco products account for their severe adverse health effects (including coronary heart disease, stroke, vascular disease, peptic ulcers, chronic lung diseases and lung cancer, and fetal brain damage and morbidity), it is the nicotine that produces potent dependency.
Existing methods – from patches to 12-step programs and chewing gum to experimental drugs – have been explored in efforts to curb nicotine dependence but the results have been less than stellar. One reason the addictive cycle is notoriously difficult to break is that only a single slip-up in abstinence from smoking is sufficient to re-infuse the brain with enough nicotine to reestablish cravings and drug-seeking behavior.
Innovative efforts have been under way for over 30 years to harness the body’s immune system to combat various drug addictions, including nicotine. The basic idea is to stimulate an immune response that would recruit antibodies capable of binding with nicotine. In this way, most or all ingested nicotine molecules would remain sequestered in the bloodstream, incapable of reaching their targets in the brain, thereby stripping them of their addictive capacity.
The approach thus far has met with mixed results. Though animal studies and human trials have demonstrated a clear correlation between high levels of nicotine antibodies and reduced nicotine dependence, vaccine effectiveness in inducing abstinence has so far been disappointing. Arranging vaccine components in just such a way as to target the immune system’s B cells, bind with them, enter the cellular interior and induce effective immunity remains a significant challenge.
The technique under study accomplishes this feat through the rational arrangement of vaccine components onto nanoscale structures, using the base-pairing properties of DNA – the biological carrier of the genetic code. The Yan lab has been on forefront of the design and fabrication of elaborate 2-D and 3-D DNA nanostructures and the rapidly advancing field is poised to enter the biomedical arena.
The use of programmable DNA nanostructures provides high precision and delicate control over the vaccine’s essential ingredients, potentially improving immunogenicity, efficacy and safety. Chang and her group will fabricate three different candidate DNA nanostructures as platforms for the vaccine’s active constituents. Two of these will be nanostructures comprising 8-arm and 12-arm branched DNA scaffolds, while the third is a DNA tetrahedral structure.
By the end of the three-year project, the group hopes to identify promising candidates for a new nicotine vaccine and advance them toward Investigational New Drug submission. The researchers emphasize that if their DNA nanotechnology approach proves successful, it could plausibly be applied to the development of future vaccines against any target of interest, including other drugs of abuse, infectious agents or tumor antigens, thereby opening an entirely new chapter in vaccine development.
This story is reprinted from material from Arizona State University, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.