In a study in published in Nature Biotechnology, investigators describe a new, more efficient way to edit genes in blood-forming or "hematopoietic" stem and progenitor cells (HSPCs).
The cell normally uses a copy of the cut DNA sequence as a template to repair the DNA break. During this process, there is the opportunity to introduce new DNA sequences or to repair mutations, effectively fooling the cell into making a genetic edit.
To provide the cell with both the targeted nuclease and the new DNA template, scientists can use a variety of delivery vehicles or vectors, including viruses and a type of genetic material known as messenger RNA (mRNA).
In the study, the team discovered a highly effective way to deliver the DNA repair template using a specific type of viral vector, known as an adeno-associated virus (AAV) serotype 6, which can naturally enter HSPCs. At the same time, they found that delivering the ZFNs as short-lived mRNA molecules allowed the DNA cutting and repair process to occur without disrupting the HSPCs. By combining these two delivery methods, the scientists were able to insert a gene at a precise site in even the most primitive human HSPCs with unprecedented efficiency rates ranging from 15 to 40 percent.
The team then transplanted these genetically edited human HSPCs into immune-deficient mice, and found that the cells thrived and differentiated into many different blood cell types -- all retaining the edits to their DNA.