Page URL:

Genome editing and CRISPR: The science of engineering the embryo

18 January 2016
By Dr Jess Buxton
Geneticist and trustee of Progress Educational Trust
Appeared in BioNews 835

CRISPR was named as Science magazine's 'Breakthrough of the Year' for 2015. This was not an entirely unexpected result – the technique was a runner-up for the same accolade in both 2012 and 2013. Despite being a relative newcomer on the genome-editing scene, CRISPR/Cas9 and related approaches have rapidly become an essential part of the molecular biologist's toolkit. They have already provided a welcome boost to diverse areas of research, ranging from cancer drug resistance and malaria control to the safer modification of pig organs for potential human transplantation. But how exactly does the CRISPR/Cas9 system work, and how might it be used in future reproductive medicine? A session at Progress Educational Trust's timely annual conference on the science and ethics of genome editing, held on 9 December 2015, aimed to answer these key questions.

The first talk was a whistle-stop tour of the basics by Dr Tony Perry of the University of Bath. He started with a brief history of the field – from the first successful gene-targeting experiments in mice in 1989 to the more recent forerunners of CRISPR/Cas9, such as ZFN and TALENs. Genome-editing techniques aim to introduce specific changes (deletions/insertions) into the DNA code. But CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats, pronounced 'crisper') has been hailed as a 'game changer' because of its superior efficiency, speed and precision compared to previous techniques.

The CRISPR/Cas9 system is adapted from a naturally occurring mechanism used by bacteria as a defence against invading viruses. It comprises an enzyme (Cas9), described by Dr Perry as 'scissors', which are targeted at one or more specific genes using a 'guide RNA'. The guide RNA acts as a molecular satnav, to ensure only the target genes are edited. Although the system is not yet precise enough for clinical use, Dr Perry predicted this would change very soon. Sure enough, two new studies show that by modifying the Cas9 enzyme, it's possible to get precise edits with no 'off target' effects (see BioNews 834). This is crucial if CRISPR/Cas9 is to be used in human treatments.

The use of CRISPR/Cas9 in gene-based therapies is probably not far off – indeed, the TALENs genome-editing technique has already been used by doctors at London's Great Ormond Street Hospital to halt the progression of an aggressive form of leukaemia in a one-year-old girl (see BioNews 827). Therapies that target the somatic cells – all body cells except for germ cells (egg, sperm and their precursors) – are likely to be relatively uncontroversial, provided their safety and efficacy can be demonstrated. The same cannot be said of germline gene therapies, which Dr Perry considered in the second part of his talk.

There are between 3000 and 5000 genetic disorders caused by alterations in single genes, many of which are known. What's more, ongoing genome sequencing efforts, such as the UK's 100,000 Genomes Project, are likely to uncover many more rare genetic causes of disease. He predicted a future in which many of these diseases might be avoided by editing the genes of human embryos before implantation.

Families affected by certain genetic conditions can already opt to use preimplantation genetic diagnosis (PGD), in which genetic testing can be used to select unaffected IVF embryos. Dr Perry argued that treating embryos to cure them of disease offered several potential advantages over selection using PGD, including the fact that sometimes there are no unaffected embryos obtained from one cycle of IVF. He also suggested that treating affected embryos using genome editing may be more acceptable to those opposed to PGD on ethical grounds, because the latter involves creating embryos that are then destroyed if they are found to carry the disease-causing mutation.

Dr Perry finished by highlighting the current public consultation on this topic, which is being run by the UK's Nuffield Council on Bioethics.

The second speaker in this session was Professor Robin Lovell-Badge of the Francis Crick Institute. Approaching the subject of germline gene therapy from a different perspective, he started by asking why shouldn't we modify our genetic make-up? We already do so in other ways, he argued, pointing to the long-running screening programmes to identify carriers of some devastating genetic diseases that are more common in Ashkenazi Jewish populations.

Scientists have previously responded to concerns expressed over the introduction of permanent genetic changes into the human germline with the argument that current methods are just too imprecise. However, Professor Lovell-Badge reiterated that with the advent of new, precise genome editing techniques such as CRISPR/Cas9, germline gene therapy was now a real possibility. He pointed out that such an approach might eventually be even safer than somatic cell therapies. If the genes of only one cell need editing (the embryo), there is a much reduced risk of off-target effects compared with somatic cell therapies in which millions of cells are typically modified.

More immediate applications for CRISPR/Cas9 lie in research into understanding genes and processes involved in reproductive health. Professor Lovell-Badge gave examples such as investigating normal embryo development in order to shed light on the causes of miscarriage, to optimise culture conditions for IVF embryos, or to enhance fertility.

He also raised the possibility of using genome editing for human enhancement – altering embryos to introduce 'human' traits such as disease resistance, dietary adaptations, increased lifespan or even 'non-human' traits, such as the ability to detect UV light or tolerate extreme temperatures. Finally, he suggested that germline alterations might be more safely and easily achieved through the modification of sperm cells rather than embryos, at least initially.

The session ended with a lively audience discussion, chaired by science writer and broadcaster Timandra Harkness. Questions ranged from the general – 'Is this the end of evolution?' – to the very specific – 'How can you spot an "off target" effect if you're aiming to cut a section of DNA out (rather than add them in)?' Only one thing seems certain, which is that we'll be hearing a lot more about genome editing and its potential implications for human health in the coming months and years.

PET would like to thank the sponsors of its conference – Merck, the Edwards and Steptoe Research Trust Fund, Ferring Pharmaceuticals, the London Women's Clinic, the Medical Research Council and Wellcome Trust.

18 December 2017 - by Dr Avi Lerner 
The Progress Educational Trust (PET)'s Annual Conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction' discussed some of the most important ethical and scientific questions facing human reproduction. The first session, chaired by Sarah Norcross, the Director of PET, tackled the very fundamentals. What is a sperm? What is an egg? And what is an embryo?...
11 April 2016 - by Ayala Ochert 
A second team in China report that they have created genetically modified human embryos, in an attempt to make them resistant to HIV, using the genome-editing technique CRISPR/Cas9...
7 March 2016 - by Kirsty Oswald 
Researchers have found that mimiviruses, a class of giant viruses, have an immune system reminiscent of the CRISPR system used by bacteria to evade infection...
8 February 2016 - by Julian Hitchcock 
Last week the front pages and airwaves filled with well-written, balanced articles about a significant development in UK embryo research. There was, however, something missing: a story...
1 February 2016 - by Dr Rebecca Dimond 
An author and a science historian host an online discussion on the promise and perils of the 'science of designer babies'...
11 January 2016 - by Paul Waldron 
Researchers have improved the genome-editing technique CRISPR/Cas9, reducing errors to nearly undetectable levels, according to a new study...
21 December 2015 - by Wendy Suffield 
At PET's recent conference, Professor Azim Surani claimed that permission to carry out experiments on embryos beyond the 14-day rule could make a huge difference to research. It may be time to review the ethical reasoning behind this time limit...
21 December 2015 - by Dr Nicoletta Charolidi 
We report from the first session of the annual conference of the Progress Educational Trust, titled 'From Three-Person IVF to Genome Editing: the Science and the Ethics of Engineering the Embryo', in which Professor Azim Surani discussed the germline...
7 December 2015 - by Dr Jane Currie 
An international summit has agreed conditions under which human genome editing, using techniques like CRISPR, should proceed...
30 November 2015 - by Dr Silvia Camporesi and Dr Lara Marks 
It is important to engage the public in the debate about genome editing as early as possible, and in a way that is as open as possible, to make sure that all possible voices are included...
to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions

Syndicate this story - click here to enquire about using this story.