Sangamo BioSciences, Inc., a leader in therapeutic genome editing, announced the publication in Nature Biotechnology of data demonstrating efficient zinc finger nuclease (ZFN)-mediated, targeted gene insertion in human hematopoietic stem and progenitor cells (HSPCs).

In addition, data published earlier this month in Nucleic Acids Research, demonstrate that similar efficiencies can be obtained in primary human T-cells. Sangamo's genome editing method provides a precisely targeted and therefore potentially safer approach than traditional randomly integrative gene therapies, such as lentiviral vectors, for the treatment of human diseases of the blood and immune system, and the generation of T-cell based cancer immunotherapies.

"These studies present new and substantial data affirming that Sangamo's ZFN genome-editing platform provides precise, robust targeted insertion of therapeutic genes, in contrast to conventional integrating vector approaches, such as lentiviral vectors that insert genes randomly," stated Edward Lanphier, Sangamo's president, and chief executive officer. "Our extensive clinical experience and a substantial body of research, documents the accuracy and efficiency of our ZFN technology, and positions it as a more versatile and potentially safer therapeutic strategy than other gene therapy and genome editing approaches. Our technology also provides an alternative manufacturing platform for cell therapies."

Researchers capitalised on the fact that ZFN-mediated genome editing requires only transient expression of the ZFNs to effect a permanent change in the genome. They used messenger RNA and electroporation to deliver the ZFNs and a non-integrating vector, an adeno-associated virus (AAV) serotype 6, to provide a therapeutic DNA sequence, a so-called "donor template", to HSPCs and CD4 and CD8 T-cells. The "donor template" can encode an entire gene that integrates at the targeted site of ZFN action. This delivery approach achieved efficiencies of gene transfer and targeted integration of the therapeutic DNA sequence, particularly in more primitive longer-lasting stem cells and T-cells, to levels that can be used therapeutically to potentially treat a range of monogenic diseases.

"Efficient targeted integration of a therapeutic gene into both hematopoietic stem cells and T-cells represents a major step forward in the quest for more precise and safer gene-based therapies," stated Michael Holmes, Ph.D., Sangamo's vice president, research, and a corresponding author on both papers.

"Importantly, in our hematopoietic stem cell work with our scientific collaborators at USC, we successfully modified a class of the most pluripotent stem cells, leading to long-term production of ZFN-modified cells across all blood cell lineages following transplantation into immune deficient mice. Our results in these two studies provide a robust strategy for additional therapeutic applications of ZFN-mediated genome editing in HSPCs and T-cells."

The stem cell study, "Homology-driven genome editing in hematopoietic stem and progenitor cells using ZFN mRNA and AAV6 donors" was carried out in collaboration with scientists in the laboratory of Paula Cannon, Ph.D., professor of molecular microbiology and immunology, pediatrics, biochemistry and molecular biology, and stem cell biology and regenerative medicine at the University of Southern California, and was published as an Advance Online Publication in Nature Biotechnology.

The T-cell study, "Highly efficient homology-driven genome editing in human T-cells by combining zinc finger nuclease mRNA and AAV6 donor delivery" was published as Advance Access in Nucleic Acids Research on November 2, 2015.