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DNA editing - a case still to be made

summer 2015

From triple helix - summer 2015 - DNA editing - a case still to be made [p05]

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Review by Peter Saunders
CMF Chief Executive

Manipulating the human germline has been off limits for decades but new technology has brought it one step closer. A new tool called Crispr enables scientists to 'edit' the genome by adding or deleting DNA sequences.

In response to a growing interest in the field, two leading science journals issued statements aimed at curbing the practice. In Nature, Edward Lanphier, a leading figure in Crispr related research, called for a voluntary moratorium on modifying the genome of eggs, sperm or embryos, saying that germline therapy 'could start us down a path towards non-therapeutic genetic enhancement'.

A similar statement in Science by experts in Crispr urged that germline modification be 'strongly discouraged', 'even in those countries with lax jurisdictions'. These cautions echoed UNESCO's statement that germline interventions 'could be contrary to human dignity'. (1)

However one month later Chinese scientists announced that they had used Crispr to genetically engineer human embryos. (2) Researchers at Sun Yat-sen University obtained defective human embryos from an IVF fertility clinic and targeted a gene which can cause beta thalassemia, a serious blood disorder. The results were unimpressive. Of 86 embryos injected only 28 had successfully spliced the target gene and only a fraction of these contained the correct replacement gene. There was also collateral damage in the form of 'off-target' mutations.

More recently, researchers in California have used a DNA editing technique successfully to treat mitochondrial disease in mice. (3)

This new research involves injecting affected embryos with RNA which leads to the production of enzymes which specifically target and remove faulty genes. (4) The treated embryos were transferred to female mice where they developed normally and resulted in healthy pups with low levels of the targeted mitochondrial DNA. These pups later gave birth to healthy offspring, demonstrating this is a viable approach for preventing transgenerational transmission of mitochondrial diseases.

Furthermore, it avoids some of the ethical problems associated with mitochondrial replacement techniques, such as cell nuclear replacement (cloning) technology, DNA donation and using DNA from three biological parents. Might this be an elegant and more ethical alternative to the controversial so-called three-parent embryo? As a technique it is certainly more about correcting a defect (restoration) than creating something altogether new (enhancement). Time will no doubt tell, but in the meantime there are big issues to address in the context of animal research, not least about safety.

References

1. Universal declaration on the human genome and human rights

2. Chinese scientists edit genes of human embryos, raising concerns. New York Times, 23 April 2015

3. Saunders P. New DNA editing technique for mitochondrial disease may render three parent embryos redundant. CMF Blogs, 30 April 2015

4. Reddy P, Ocampo A et al. Selective elimination of mitochondrial mutations in the germline by genome editing. Cell 2015;161(3):459– 469



Article written by Peter Saunders

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