AAV-directed persistent expression of a gene encoding anti-nicotine antibody for smoking cessation.
| Publication Type | Academic Article |
| Authors | Hicks M, Rosenberg J, De B, Pagovich O, Young C, Qiu J, Kaminsky S, Hackett N, Worgall S, Janda K, Davisson R, Crystal R |
| Journal | Sci Transl Med |
| Volume | 4 |
| Issue | 140 |
| Pagination | 140ra87 |
| Date Published | 06/27/2012 |
| ISSN | 1946-6242 |
| Keywords | Antibodies, Monoclonal, Dependovirus, Nicotine, Smoking Cessation |
| Abstract | Current strategies to help tobacco smokers quit have limited success as a result of the addictive properties of the nicotine in cigarette smoke. We hypothesized that a single administration of an adeno-associated virus (AAV) gene transfer vector expressing high levels of an anti-nicotine antibody would persistently prevent nicotine from reaching its receptors in the brain. To test this hypothesis, we constructed an AAVrh.10 vector that expressed a full-length, high-affinity, anti-nicotine antibody derived from the Fab fragment of the anti-nicotine monoclonal antibody NIC9D9 (AAVantiNic). In mice treated with this vector, blood concentrations of the anti-nicotine antibody were dose-dependent, and the antibody showed high specificity and affinity for nicotine. The antibody shielded the brain from systemically administered nicotine, reducing brain nicotine concentrations to 15% of those in naïve mice. The amount of nicotine sequestered in the serum of vector-treated mice was more than seven times greater than that in untreated mice, with 83% of serum nicotine bound to immunoglobulin G. Treatment with the AAVantiNic vector blocked nicotine-mediated alterations in arterial blood pressure, heart rate, and locomotor activity. In summary, a single administration of a gene transfer vector expressing a high-affinity anti-nicotine monoclonal antibody elicited persistent (18 weeks), high titers of an anti-nicotine antibody that obviated the physiologic effects of nicotine. If this degree of efficacy translates to humans, AAVantiNic could be an effective preventative therapy for nicotine addiction. |
| DOI | 10.1126/scitranslmed.3003611 |
| PubMed ID | 22745437 |
| PubMed Central ID | PMC3622954 |