Gene therapy is a method of correcting faulty genes responsible for certain diseases, particularly cancers. It involves using a carrier, or 'vector', to insert new genetic material to mend a faulty gene in the affected cells of the person or 'host'. To achieve this, the vector must be able to survive the host's various defence systems and travel through the cell to its nucleus, which holds the host's genes.
Gene therapy has great potential, but currently there are no treatments available on the market as the method is complicated and is still being investigated.
The study by pharmacy researchers focuses on Schistosoma mansoni - a worm which is rife in Asia, Africa and South America - that penetrates human skin to infect the lungs, liver, intestines, bladder, and possibly other organs. The resulting disease (schistosomiasis) is second only to malaria as the most devastating parasitic disease in tropical countries.
The study focused on a protein called IPSE, which is released in large amounts by the worm's eggs into the surrounding tissues, and enters host cells. The study shows that once inside host cells, IPSE rapidly enters the nucleus and can bind to DNA. A very small portion of IPSE can drag much larger proteins through the nuclear pores into the nucleus with it.
IPSE therefore has a natural ability to pass right into the cell nucleus and bind with the host genetic material, which makes it a promising option for gene delivery.
University of Nottingham School of Pharmacy PhD student, Ishwinder Kaur, said: "The worm attracted the team's interest because to survive in their hosts, successful parasites have evolved sophisticated ways of evading and/or manipulating their host's immune response. Schistosomes can survive for more than a decade in their host. So, studying how the parasite interacts with its host's immune system can give us valuable clues as to how to exploit strategies honed by millions of years of evolution."
"It's a very exciting find, but much more research needs to be carried out to ensure that it has no unwanted effects on host cells."
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It was found that both SNPs were associated with BMI only in individuals who had low physical activity scores for their age and sex, and had no effect on those with above-average physical activity scores.
The researchers say activity levels in the 'high-activity' stratum were approximately 900 calories higher than in the 'low-activity' stratum, which, depending on body size, corresponds to about three to four hours of moderately intensive physical activity, such as brisk walking, house cleaning or gardening.
They say the study showed that the FTO gene with its increased BMI and obesity risk is not significant in people who are very physically active and may have important implications in targeting personalized lifestyle recommendations to prevent obesity in genetically susceptible individuals.
Dr. Soren Snitker, who led the research, says the results strongly suggest that the increased risk of obesity due to genetic susceptibility can be blunted through physical activity.
The research is published in the current issue of the Archives of Internal Medicine.