New method for inserting genes developed by UH Manoa scientists

University of Hawaiʻi at Mānoa
Posted: Apr 30, 2010

Diagram depicting insertion of the piggyBac transposon into the host cell genome.
Diagram depicting insertion of the piggyBac transposon into the host cell genome.
Scientists at the University of Hawai’i at Mānoa, along with domestic and international collaborators, have significantly improved the way in which genes can be inserted into the chromosomes of host cells, an approach that can be used for gene therapy. The new technique is reported by Dr. Stefan Moisyadi and his colleagues at the Institute for Biogenesis Research (IBR) at UH Mānoa’s John A. Burns School of Medicine. The non-viral gene insertion technology was published in an April 19, 2010, online article in the Proceedings of the National Academy of Sciences (PNAS).  
This method uses a jumping gene, called a transposon. “Originally discovered in a moth, the transposon has many advantages over traditional viral methods,” said Dr. Moisyadi. “For example, it is able to insert larger genes and potentially a decreased chance of adverse immune response.”
More importantly, non-viral methods lacked the ability to control the jumping of the transgene after its insertion. Dr. Moisyadi and his team have developed a method to prevent this jumping.
Dr. Moisyadi is working on a transposon called piggyBac, originally discovered at the University of Notre Dame by Dr. Malcolm Fraser. PiggyBac is the most efficient integrating non-viral method with many advantages over other non-viral methods. The UH Mānoa discovery has the potential of greatly influencing the field, by being applied in future gene therapy trials with transposons.
Gene therapy is a technique for correcting defective genes responsible for disease development by replacing the faulty gene through the integration of a new corrected gene, called the transgene. This therapy holds promise for treating a wide range of diseases, including diabetes, cancer, cystic fibrosis, heart disease, hemophilia and AIDS. Gene therapy trials have met many setbacks due to technical and scientific difficulties which, in some instances, have resulted in the death of a patient.
Dr. Moisyadi and his collaborators are currently working on further improvements to the safety features of transposon-based gene therapy, such as targeting the transgene to specific sites within the genome. These new developments have the potential to decrease the risk of inducing cancer by mutagenesis, as has been observed with viral gene therapy systems currently under use. The IBR team also is presently testing the possibility of using jumping genes for breast cancer treatment.