Genome editing not ready to be tried safely and effectively in humans – experts

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15:43pm, Thu 03 Sep 2020
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Genome editing is not ready to be tried safely and effectively in humans, experts have said.

The method should not be used to create a pregnancy until it is established that precise genomic changes can be made without introducing undesired changes.

This is something that no genome editing technology has been able to do, says a new report by an international commission of the US National Academy of Medicine, US National Academy of Sciences, and the UK’s Royal Society.

Heritable human genome editing (HHGE)  is when the DNA of a human embryo, sperm or egg is deliberately altered to influence the characteristics of a future individual.

Any initial uses of HHGE should proceed incrementally and cautiously, and provide the most favourable balance of potential benefits and harms

Heritable genome edits can be passed down to future generations, raising scientific and medical considerations, as well as ethical, moral, and societal issues.

Initial clinical uses, if permitted, should be limited to serious single-gene diseases, which result from the mutation of one or both copies of a single gene, the report says.

This includes diseases like cystic fibrosis, thalassemia, sickle cell anemia, and Tay-Sachs disease, the report says.

It also describes cases when HHGE might be considered.

These are when, without the procedure, prospective parents at known risk of transmitting a serious monogenic disease have no option or extremely poor options for having a biologically related child who is not genetically affected.

Commission co-chairman, Richard Lifton, president of the Rockefeller University, New York City, said: “Any initial uses of HHGE should proceed incrementally and cautiously, and provide the most favourable balance of potential benefits and harms.

“For the prevention of serious monogenic diseases, the commission has defined a responsible clinical translational pathway from rigorous preclinical research that determines whether and how editing can be performed efficiently and with high accuracy, to clinical application.”

The report says it is not currently possible to define responsible translational pathways from research to clinical application for other potential uses of HHGE.

It adds that the uses, circumstances, and considerations differ widely, as do the technical advances that would be needed to make additional clinical uses feasible.

Commission co-chairwoman, Kay Davies, professor of genetics at the MDUK Oxford Neuromuscular Centre at the University of Oxford, said: “Should they ever be used, it is vitally important that these technologies are used for medically justified interventions, based on a rigorous understanding of how the pathogenic variant leads to disease.

“More research is needed into the technology of genome editing in human embryos, to ensure that precise changes can be made without undesired off-target effects.

“International cooperation and open discussion of all aspects of genome editing will be essential.”

The report also suggests that before any clinical use of HHGE, an independent, multidisciplinary International Scientific Advisory Panel should be established to continuously assess the state of the scientific evidence.

In order to proceed with any HHGE applications beyond the initial uses, the commission recommends the creation of an international body to make recommendations concerning any proposed new category of use, and to advise on scientific and clinical benefits and risks.

The international commission was formed in the aftermath of the 2018 International Summit on Human Genome Editing held in Hong Kong.

At the summit a researcher from China announced that twins had been born following editing he had performed on early embryos, despite broad agreement in the scientific and clinical communities that it was premature and irresponsible to undertake heritable human genome editing.

The commission’s goal was to define specific criteria and standards that would be required before HHGE could be considered for clinical use.

– A Translational Pathway from Research to Clinical Use

The report describes a translational pathway for initial clinical use of HHGE.

It identifies a number of requirements for preclinical evidence that should be met to demonstrate that embryos have been correctly edited as intended, before any attempt is made to establish a pregnancy with edited embryos.

The in vitro development of edited human embryos should also be evaluated prior to establishing a pregnancy to ensure that they meet developmental milestones.

A biopsy should demonstrate that the intended edit is present in all biopsied cells, with no evidence of unintended edits.

The experts say monitoring the resulting pregnancy is vital, if regulatory approval to establish a pregnancy is granted.

Additionally, research should continue to evaluate the potential use of stem cells in producing functional human eggs or sperm, the report says.

This technique could reduce or eliminate the need for genome editing at the time of or after fertilisation, researchers explain.

However, this type of HHGE should also be carefully evaluated, as it raises its own distinct medical, ethical, and societal issues, the experts say.

Asked how far the technology is from being able to be safely used, Professor Haoyi Wang, of the state key laboratory of stem cell and reproductive biology, Chinese Academy of Sciences, said: “It is a little bit difficult to predict, but I’m quite optimistic that the technology will achieve a much higher specificity, and reducing the mosaicism to a very low level, in the very near future – a few years maybe.”

But he added that the genomic sequencing technology of the single cell, which was also necessary, may take some more time.

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