'There are lots of unanswered questions,' said embryologist Dr Anthony Perry of the University of Bath, who was not one of the six authors.
A team of scientists led by Dr Shoukhrat Mitalipov of the Oregon Health and Science University, Portland, USA made headline news in August (see BioNews 912) when they reported successful correction of a paternal disease-causing mutation in human embryos. The team had injected eggs with both the CRISPR/Cas9 components and sperm carrying the mutation at the same time. An unexpected and key finding of their study was that CRISPR/Cas9 had apparently replaced the disease-causing gene using the maternal gene, rather than the template healthy gene copies provided.
However, Dr Dieter Egli of Columbia University, New York and others say there is no plausible biological mechanism for this to happen. They say it is more likely that CRISPR/Cas9 could have caused a large deletion in the paternal gene, which was self-repaired by the cell but prevented the mutation from showing up in the genetic assay.
'It’s very difficult to conceive how recombination can occur between parental genomes across these huge cellular distances,' he said.
Dr Junjiu Huang of Sun Yat-Sen University, China, whose team led the world's first human embryo editing study (see BioNews 799), agreed with this suggestion. He told Science Magazine that while his group's study had shown another gene related to the CRISPR-targeted gene had been used as a template, both genes had been located on the same chromosome.
Another theory suggested by Dr Egli's group is that the embryos developed without contribution from the paternal genes, which can happen in some IVF procedures. Dr Mitalipov's team had shown that the paternal genome was present in only two out of six embryonic stem cell lines made from the genome-edited embryos.
Dr Egli's group intend to submit a further article to Nature.
Dr Mitalipov has released a statement saying his team intended to publish a response to each author's concerns.
'We recognize that these results must be confirmed by additional studies,' said Dr Mitalipov, and 'encourage other scientists to reproduce our findings by conducting their own experiments on human embryos and publishing their results.'
The latest developments in genome editing and embryo research will be discussed at the session 'What Next for Genome Editing? Politics and the Public', at the Progress Educational Trust's upcoming public conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction'.
The conference is taking place in London on Friday 8 December 2017. Full details - including sessions, speakers and how to book your place - can be found here.