Development of Novel Site-Specific Recombination Based Nanotechnology for Human Genetic Diseases and Cancer Therapies
HK022 bacteriophage site specific recombinase Integrase is the tool for human genome manipulation and gene therapy. Site specific recombinases (SSRs) catalase the site-specific recombination reaction between two specific short DNA sequences of 30-40 bp that serve as recombination sites that included integration, excision and inversion. These enzymes are widely used for the genome manipulations and gene therapy. E. coli HK022 bacteriophage site specific recombinase Integrase (HK-Int) belongs to the tyrosine family of SSRs and catalyzes the phage integration into E. coli chromosome and prophage excision. We have previously adopted the HK-Int for genome manipulation in plants, Cyanobacteria and human cells.
We have found that the HK-Int can utilize endogenous human attB sites that flank human deleterious mutations. The main goal of this research is to adopt the HK-Int for curing human hereditary diseases using the Recombinase Mediated Cassette Exchange reaction. We expect that our research will lead to the development of novel efficient human genome manipulation technology that will be useful for gene therapy of hereditary diseases.
We have developed a new cancer specific cells killing binary system activated by the HK- Int. We have validated the cancer cells killing activity of our new binary system in LLC1 Katushka lung cancer mice using a diphtheria toxin gene. We expect that our system will be used in the future for the establishment of a specific cancer cells killing system for lung cancer, as well as for other different types of cancer.