They have devised a vaccine that floods the body with an antibody to assault nicotine entering the body.
A study in mice, published in Science Translational Medicine, showed levels of the chemical in the brain were reduced by 85% after vaccination.
Years of research are still needed before it could be tested on people.
However, lead researcher Prof Ronald Crystal is convinced there will be benefits.
"As far as we can see, the best way to treat chronic nicotine addiction from smoking is to have these Pacman-like antibodies on patrol, clearing the blood as needed before nicotine can have any biological effect."
Other "smoking vaccines" have been developed that train the immune system to produce antibodies that bind to nicotine - it is the same method used to vaccinate against diseases. The challenge has been to produce enough antibodies to stop the drug entering the brain and delivering its pleasurable hit.
Scientists at Weill Cornell Medical College have used a completely different approach, a gene-therapy vaccine, which they say is more promising.
Prof Ronald CrystalWeill Cornell Medical College
If they start smoking again, they will receive no pleasure from it due to the nicotine vaccine, and that can help them kick the habit”
A genetically modified virus containing the instructions for making nicotine antibodies is used to infect the liver. This turns the organ into a factory producing the antibodies.
The research team compared the amount of nicotine in the brains of normal mice with those that had been immunised. After being injected with nicotine, the vaccinated mice had nicotine levels 85% lower.
It is not known if this could be repeated in humans or if this level of reduction would be enough to help people quit.
Prof Crystal said that if such a vaccine could be developed then people "will know if they start smoking again, they will receive no pleasure from it due to the nicotine vaccine, and that can help them kick the habit".
He added: "We are very hopeful that this kind of vaccine strategy can finally help the millions of smokers who have tried to stop, exhausting all the methods on the market today, but find their nicotine addiction to be strong enough to overcome these current approaches."
'Impressive and intriguing'
There are also issues around the safety of gene therapy in humans that will need to be answered.
Professor of genetics at the University of Kent, Darren Griffin, said the findings were "impressive and intriguing with great potential" but cautioned there were still many issues which needed addressing.
He said the main issue "is whether the observed biochemical effects in lab mice genuinely translate to a reduced addiction in humans given that such addictions can be both physical and psychological".
Dr Simon Waddington, from University College London, said: "The technology underpinning gene therapy is improving all the time and it is encouraging to see these preliminary results that indicate it could be used to address nicotine addiction, which is damaging to the nation's health and a drain on the health service economy."
If such a vaccine was developed it could also raise ethical questions about vaccinating people, possibly in childhood, before they even started smoking.