January 19, 2015

expert reaction to new study reporting new ‘molecular scissors’ technique in mice

A study published in the journal Scientific Reports has described the use of a technique to edit specific genes in eggs or sperm at the time of fertilisation, which the research team suggest may have potentially have therapeutic benefits.

Prof. Ian Jackson, Professor and Head of Medical and Developmental Genetics, MRC Human Genetics Unit (HGU), said:

“This paper is analysing the effectiveness of a technique known as Cas9/CRISPR in editing the genome of mouse embryos. In just a few years since it was first described this technique has been adopted by many labs around the world, including my own and half a dozen in my Institute, who are using this technique to rapidly produce mouse mutations in specific genes. The paper has useful data on the relative ease of editing the DNA originating from egg or sperm, and indicates that editing the sperm genome can be highly effective. The technique is already in use for engineering livestock (pigs, sheep, cattle) genomes, at several Institutes. A group in China has used it to engineer a monkey genome. The press release (but not the paper) suggests that this makes possible engineering livestock for organs that will not be rejected. This idea has been around for a long time, and there were companies in the 80s and 90s trying exactly this with pigs, when it was much more difficult, and there was a huge amount of discussion of the ethics of this. As the authors also say in the paper it is also theoretically possible to use this new technique it to cure human genetic mutations and it might be used in the future once side effects have been better characterised, but this is a long way off and there are legal and ethical considerations.

“The Science Media Centre dealt with the idea of using CRISPR on human embryos on 7th November 2013 http://www.sciencemediacentre.org/expert-reaction-to-comment-on-independent-splash-on-crispr/.”

Prof. Robin Lovell-Badge, Head of Developmental Genetics, MRC National Institute for Medical Research (NIMR), said:

“This is a well-conducted piece of research and the results are interesting with respect to the details of genome editing using CRISPR/Cas9 during very early embryo development. However, the authors only explored the generation of mutations, which is far easier and more efficient than use of the methods to correct gene defects. Moreover, there will be relatively few cases in humans where even this is necessary, given that it would be more straightforward to use preimplantation genetic diagnosis to screen for embryos that lack the mutation. About the only situation where gene correction might be useful, and assuming it can be made to work efficiently and precisely, without damaging DNA elsewhere, is where the father has very low fertility due to a mutation on the Y chromosome. Intracytoplasmic sperm injection into the egg is used to allow such patients to have children, but any son born will also have low fertility. Correcting the mutation would overcome the need to use ICSI in subsequent generations. However, as the authors state, any application of these gene editing techniques in humans would require extensive public debate and assessment of safety. Any “potential to prevent genetic diseases prior to conception” is a long way off.”

‘Asymmetric parental genome engineering by Cas9 during mouse meiotic exit’ by Toru Suzuki et al. published in Scientific Reports on Tuesday 23 December 2014.

Declared interests

Prof Ian Jackson is on the Board of the NC3Rs.