In gene therapy, one or more desired genes are introduced into an adenovirus, a virus that causes the common cold, which is then administered to the patient. Once in the body, the virus enters targeted cells and delivers the desired genes. In heart disease patients, for example, the virus delivers genes that trigger the growth of new blood vessels in damaged heart muscle.
The virus is not able to reproduce and cause disease so scientists have been trying to use the adenovirus but administering the virus to patients causes an inflammatory reaction; that reaction aids in the use of the virus in vaccines but limits its use for gene therapies. In extreme cases, this can endanger the patient and in one highly publicized case, a University of Pennsylvania gene therapy patient named Jesse Gelsinger died from a massive immune response triggered by the use of the adenovirus.
In vaccines, the adenovirus delivers one or more genes. These genes instruct cells to produce a specific protein, which is normally part of the targeted pathogen. This protein, in turn, jump-starts the patient's immune system to attack a specific pathogen, such as the bacterium that causes tuberculosis or the parasite that causes malaria. Here, the inflammatory immune response has the beneficial effect of revving up the immune system to attack germs.
A new study in the Journal of Virology provides new insights into how the adenovirus triggers an immune response. It involved immune cells from humans and mice and they discovered how cells sense the adenovirus as it enters a cell, which triggers the immune response.
"These results will help with future studies of innate immune responses to adenovirus," Wiethoff and colleagues wrote. "Additionally, our understanding of this process could allow us to either enhance or attenuate [weaken] the innate immune response to adenovirus to generate novel vectors for gene therapy and vaccination."