Everything you need to know about gene editing

Gene editing is nothing new.

Researchers in every field – from agriculture to medicine – have been tinkering with genetic codes for the past three decades in an attempt to improve human health and enhance global food security.

CRISPR-Cas9 is the latest cut-and-paste genetics tool to excite scientists due to its high precision and accuracy.

Unlike previous gene-editing tools such as zinc finger nucleases (ZFNs) and TALE nucleases (TALENs), which were all the rage a few years ago, the CRISPR-Cas9 system is cheap, as well as quick and easy to use.

Just like a pair of molecular scissors, the CRISPR-Cas9 method cuts DNA at a precise location, allowing new bits of DNA to be added, deleted or replaced in the genome of a living organism.

The CRISPR system as we know it today is made up of three crucial molecules: one to cut, one to guide the cutting enzyme to its target, and one to activate the cutting enzyme.

DNA sequences called CRISPRs, which stands for clustered regularly interspaced short palindromic repeats, were first reported in bacteria by Japanese scientists in 1987.

Fast forward to 2012, and researchers announce that they have repurposed this molecular system, which bacteria use to fend off viruses, to edit genes.

Though relatively rare, millions of people worldwide are affected by genetic conditions, including Cystic Fibrosis and Huntington’s Disease.

Most have no cure and where treatment is available, more often than not, it is to manage the symptoms of the condition, rather than eliminate it altogether.

Gene-editing technologies such as CRISPR-Cas9 represent a promising way of addressing the cause, not just the symptoms, of these debilitating illnesses.

CRISPR-Cas9 has already shown promise as a potential treatment in human somatic (non-reproductive) cells.

Several teams around the world are already using the system to develop therapies for a range of conditions.

One example is a type of gene therapy where cells are taken from the body and their DNA edited to correct a fault, or add a new function, before being put back into the patient. Work is underway to apply this approach to bone-marrow cells as a potential treatment for sickle cell disease and thalassaemia, which are both blood abnormalities.

As with any new technology, huge potential also comes with pressing concerns.

Until April 2015, when a group led by Junjiu Huang at Sun Yat-sen University in Guangzhou, China, described the use of CRISPR-Cas9 to edit the genomes of human embryos, the technique had almost always been carried out on animal cells.

While Huang’s group used the CRISPR-Cas9 system in non-viable embryos, which could not have progressed to live births, the publication of the work sparked fresh debate over the ethics of editing human germ (reproductive) cells that could be passed on to future generations, and whether China had become a Wild West in the application of the technique.

While editing human germ cells could be seen as one of the most exciting implications of CRISPR-Cas9, due to the fact that edits will pass between generations and eradicate potentially life-limiting and fatal genetic conditions that have affected families for generations, edited changes could cause unintended consequences.

Precision

Compared to its predecessors, CRISPR-Cas9 is hailed for its precision and accuracy; yet there are still concerns about what would happen if the system missed its target, which has been reported as happening.

Taking things one step further is the that techniques such as CRISPR-Cas9 will lead to designer babies, with parents picking and choosing traits for their child.

CRISPR-Cas9 is currently only used in research settings, yet laws on editing human germ cells, even for research purposes, vary across the world.

In some countries, experimenting with human embryos is a criminal offence, whereas in others, almost anything goes.

Not only are some countries more accepting than others, but the mechanisms of regulation and enforcement differ across borders. The US, for example, does not allow the use of federal funds to modify human embryos, but there are no outright bans on gene editing.

In the UK, an independent body considers applications for human gene editing on a case-by-case basis.

In January 2016, researchers at the Crick Institute in London were granted approval to use CRISPR-Cas9 to alter genes in human embryos to study early development – the first endorsement of such research by a national regulatory authority.

Unenforceable

Countries such as China, Japan, India and Ireland, on the other hand, have guidelines that restrict the editing of human embryos, but they are largely unenforceable.

Regulations will need to keep up with the rapid pace of change that CRISPR-Cas9 has brought to research labs around the world.

Developing international guidelines, even if not enforceable, could be a step towards establishing coherent national frameworks.

This work is, in part, already in progress.

In the wake of the research carried out in China on human embryos in 2015, the International Summit on Human Gene Editing was organised by the US national academies of sciences and medicine, the Royal Society in London and the Chinese Academy of Sciences (CAS).

A statement released at the end of the meeting did not condemn gene editing research on human embryos that are not intended for establishing pregnancy, but agreed that a host of ethical and safety issues needed to be resolved before the technology moved to the clinic.