Scientists question CRISPR human embryo editing claims

A paper published in the journal Nature on the 2nd August described how a gene editing tool CRISPR could be used to correct a genetic mutation that leads to a heart condition. This team had performed the genetic editing on the gene sequences in dozens of viable human embryos to attempt to prevent a genetic heart condition called hypertrophic cardiomyopathy.

Reproductive biologists at the Oregon Health Sciences Center in Portland, unlike all their predecessors who used this tool for genetic editing, had shown that this technique had a high success rate at correcting a disease-causing mutation in a gene.

The authors of the paper claimed that CRISPR-Cas9 genome editing tool could successfully replace a mutant version of the MYBPC3 gene which was present on the sperm with a same healthy copy that it obtained from the egg cell. When this modified sperm and the normal egg cell combine, they thus make an embryo with two normal copies of the gene. This eliminates the possibility of the disease. Earlier the team was trying to insert a healthy version of the gene into the sperm. Their experiments showed that the corrected embryos worked best when they received a healthy copy from the mother’s egg cell rather than externally.

Now a team of stem-cell scientists and geneticists are questioning the research, asking if the mutations were actually eliminated by the procedure.

This new report in open-access preprint server bioRxiv and led by Dieter Egli, a stem-cell scientist at Columbia University in New York City along with developmental biologist Maria Jasin, at Memorial Sloan Kettering Cancer Center in New York City and George Church, a geneticist at Harvard Medical School in Boston, Massachusetts, raises questions.

The researchers doubt that the steps outlined by Mitalipov’s team actually occurred. Egli and Jasin explain that there can be no plausible biological mechanism that can explain how a genetic mutation in sperm could be replaced by one from the egg cell. They add that the researchers probably failed to fix the mutation and could not detect it because of inadequate genetics assay.

Mitalipov said in a statement that their study has been submitted to Nature and the doubts raised by Egli and colleagues do not have any results to substantiate their criticism but they are using alternative explanations based on speculation.

However Egli and colleagues are not alone in their skepticism. Reproductive biologist Anthony Perry, at the University Of Bath, UK, also believes Mitalipov might be wrong. He explained that after fertilization, the genes of the egg and the sperm remain at the opposite ends of the egg cell covered in a membrane for several hours. This would make it difficult for CRISPR to correct the mutations in the sperm after making a copy from the maternal gene using the process of homologous recombination. He said that the cellular distance was too big for a recombination to occur.

According to Egli’s paper, CRISPR could have introduced a large deleted area in the sperm cell which the genetic assay of the Mitalipov’s team failed to detect. The Cas9 enzyme breaks DNA strands and this damage is quickly put together resulting in missing sequences of genes called deletions.

Gaetano Burgio, a geneticist at the Australian National University in Canberra also agrees with Egli’s views. Developmental biologist Robin Lovell-Badge, at the Francis Crick Institute in London however wants to be sure of the procedure and its outcome from Mitalipov before deciding against his favor.

Mitalipov’s team has agreed to reply to the critiques on each count in the form of a “formal peer-reviewed response” in a journal in a few weeks.

References

Dr. Ananya Mandal

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Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.

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