|
|
|
|
|
Jumping Genes Could Cure Genetic MaladiesThey could be improved to be more efficient than viruses |
By Stefan Anitei, Science Editor
26th of September 2006, 14:18 GMT
Adjust text size:  
|
| |
A jumping gene first found in a moth species proved to be safer than viruses in gene therapy. They compared the capacity of the four best studied jumping genes (called also transposons) to insert themselves into a cell's DNA at the right point to produce a desired change, such as making the cell resistant to damage from radiation therapy.
The piggyBac transposon was 5 to 10 times better than the other transposons in several mammalian cell lines, including three human ones. "If we want to add a therapeutic gene, we can put it within the transposon and use it to deliver the gene into the cell," says Dr. Joseph M. Kaminski, radiation oncologist at the Medical College of Georgia Cancer Center. "You can use these wherever retroviruses have been used."
The other transposons from the study were: hyperactive Sleeping Beauty, first found "asleep" in fish (previously believed to be the best jumping gene for gene therapy), Tol2, another fish transposon, and Mos1, found in insects.
The piggyBac transposon, which has close relatives in the human genome, is widely used to genetically modify insects. Sleeping Beauty has been
used widely in experimental gene therapy of hereditary diseases, including hemophilia, in a mouse model.
Scientists compared the action of transposons using them to deliver an antibiotic-resistant gene. "It's a way of screening and seeing which transposon is better," Dr. Kaminski says.
Even if piggyBac is not as efficient as a virus, it is much more effective than Sleeping Beauty for this task. "Sleeping Beauty has captured the field as far as transposons to be used in mammals," says Dr. Stefan Moisyadi, molecular biologist, at the University of Hawaii.
"But by comparing different transposons, we showed Sleeping Beauty is far inferior to piggyBac."
Viruses are used in gene therapy for more than 20 years, because of their capacity of getting inside cells and inserting themselves in DNA. But they also have a dark side. Virus gene therapy trials have been stopped, because of major complications, including deaths. E.g., patients could die because of immune response to adenoviruses and a study revealed three children developed leukemia because the virus insertion in a wrong point activated a cancer-causing gene. "With viruses, you don't have control," says Dr. Kaminski.
"People have tried to modify viruses for site-specific integration and have not been very successful. Once they get into the cell, they can insert wherever they want."
Dr. Kaminski hypothesized in previous studies that the integration site for transposons could be selected.
"Typically, viruses and transposons will integrate anywhere along the genome," he says.
"If they integrate anywhere, it can obviously cause harm. If we can target the integration, be able to insert the gene at a safe spot in the genome, that would be beneficial."
"I think it's a short step to take it to a targeting mechanism we can use in humans."says Dr. Moisyadi
Transposons are cheaper to produce, so, more available to the population. "For example, retroviruses use RNA to make DNA, an error-prone process that must occur before integration," Dr. Kaminski says.
Another lack of the viruses is their disability to carry larger genes, such as the dystrophin gene, which could help correct muscular dystrophy. Unlike retroviruses, transposons have to be wrapped with lipid to get into cells. But there is hope. "We could potentially make a hyperactive version of piggyBac, like they did for Sleeping Beauty, which might be as good or better than retroviruses," Dr. Kaminski says.
"I think we'll do it or somebody will. I think it's a safer method."
"At the moment, unless something new comes out, it's the only way to go because viruses have been killing people," says Dr. Moisyadi, who has avoided viruses in his transgenesis studies. "One of our next goals is to use transposons to deliver a radio-protective gene, called manganese superoxide dismutase, to potentially protect normal tissue from radiation damage", Dr. Kaminski says.
Cancer gene therapy will focus on this type of modification of normal tissue for protective purposes, as well as manipulating the immune response. Gene therapy has broad applications for curing single gene disorders, such as hemophilia, sickle cell disease and muscular dystrophy, but also in cancer (modifying tissue for protective purposes or manipulating the immune response).
|
|
| Rating: |
|
Fair (2.0/5) |
6 vote(s) so far |
|
|
|
|
User opinions: |
 No user comments yet.  Be the first to express your opinion using the form below! |
|
|
