Finding Safe Harbor in the Human Genome

A novel framework for identifying genomic safe harbors (GSHs) is reported in Genome Biology this week, representing a new tool for genomic engineering studies and gene therapies. GSHs are regions of the genome that can maintain transgene expression without affecting host cell function and thus offer a way to improve the safety and efficiency of genome engineering. However, only a few GSHs have been identified and finding others remains technically challenging. To address this, a team led by researchers at St. Jude Children's Research Hospital developed a method for GSH identification that integrates information from polymorphic mobile element insertions that naturally occur in human populations, epigenomic signatures, and 3D chromatin organization. They applied their approach to data from the 1000 Genomes Project and the Genotype-Tissue Expression Project to reveal 19 blood GSH candidate loci. For three of these, they demonstrated the stable expression of transgenes without alternating transcription of nearby genes in erythroid cells. The researchers also presented a computer program for knowledge-based tissue-specific GSH selection. "In combination with the fast-growing genome engineering technologies, our approach has the potential to improve the overall safety and efficiency of gene and cell-based therapy in the near future," the authors write.