Is Gene Editing the Future of Gene Therapy?

Posted by The Evidence Blog on March 11, 2014

By Diane Allingham-Hawkins, PhD, FCCMG, FACMG, Senior Director, Genetic Test Evaluation Program and Technical Editing

As reported this week in the New England Journal of Medicine, researchers at the University of Pennsylvania have invented a new method that successfully and safely “edited” a key gene involved in HIV infection and decreased the level of HIV DNA in the blood of most of the patients enrolled in the small phase I clinical trial.

In the 1980s, gene therapy was considered the brave new world for curing genetic disorders. The concept seemed simple enough—replace a defective gene in the cells of affected individuals and cure the disease. In reality, getting the right gene into the right cell type at the right time in human development (i.e., embryonic, fetal, childhood, or adulthood stages of development) to cure the disease is much more complex than initially thought. Some genes are only expressed in certain tissues and/or at certain times in development. Expressing them at uncontrolled levels or in other cell types can lead to unintended consequences. A famous cover of Nature magazine in 1982 showed mouse littermates, one of which had been engineered to contain a rat growth hormone gene. The result? A really big mouse! Of course, gene therapy has come a long way since those early experiments and modest success has been reported in some diseases.

Gene editing, as the process has been dubbed by researchers, relies on zinc finger nucleases (ZFN) to specifically target genes of interest. In the Penn study, ZFN was used to deactivate the CCR5 gene in the CD4 T-cells of 12 patients with HIV. CCR5 encodes a cell surface receptor that allows HIV to enter vulnerable cells. The modified T cells were then infused back into the patients and the levels of HIV DNA and RNA were monitored. Although the primary outcome was safety of the procedure, researchers were also able to demonstrate a sustained retention of the modified T cells in the blood of participants and most patients showed a decrease in the blood level of HIV DNA. The procedure appeared to be relatively safe with just one serious adverse event, which was attributed to a transfusion reaction.

Of course, this is a small, single study and the first demonstration that gene editing is feasible. Much more work is needed to establish the safety and efficacy of gene editing, as well as show that patient outcomes can be meaningfully affected by its use. This is an interesting and exciting development in the field of gene therapy that we at Hayes will continue to watch carefully!

Topics: Hayes Blog, Genetic Testing

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