What do we mean by ‘genome editing’?
Genome editing is the deliberate, targeted alteration of a DNA molecule in a living cell. A large and growing family of techniques, developed over the last 15 years, can achieve this with precision and reliability. They include Zinc Finger Nucleases, TALENs and RNA- (CRISPR-) guided endonucleases, such as CRISPR-Cas9.[i] A common approach uses a protein to cut the DNA molecule at the target site and then utilises repair mechanisms that exist naturally within every cell to re-join the severed ends. Other approaches target sequences without causing a break in the DNA molecule, either to substitute individual bases (units of the molecular code) or to modify how sections of DNA are expressed.[ii] These different approaches, which are still evolving, offer ways either to disrupt the biological function of a known DNA sequence or to create a new function by inserting an extra sequence.
Among genome editing technologies, the CRISPR-based methods that have emerged over the last few years are particularly promising owing to their relative efficiency, low cost and ease of use. They also make it possible to edit multiple places in the genome in a single procedure. This has led to their rapid uptake across a range of areas of biological research. Many people believe these techniques have the potential to give rise to new technologies that could transform animal farming. The CRISPR family of techniques has been subject to a number of refinements and research continues to discover new approaches and new applications. By ‘genome editing’, therefore, we do not mean to refer to a particular technique but, rather, to the idea of using molecular approaches to directly and intentionally alter genome sequences or gene expression.
Why is genome editing relevant to farmed animals?
Animals have been domesticated by humans for meat, dairy products, clothing and as service animals for around 11,000 years. Over long periods of time, selective breeding has led to the development of animals with features that have benefitted humans, such as increased muscle mass, fast growth rate, high fertility, docility and resistance to disease. These features also have implications for the welfare of the animals themselves, which may be positive or negative. As most of these features are genetically conditioned, this selective procedure has implicitly involved alterations to the animals’ characteristic genomes.
With the advent of genetic testing and genome sequencing it has become possible to understand the relationship between some specific genetic variants and observable features. This knowledge could be used, first, to select animals with desirable genetic traits and, then to use genetic techniques to introduce new traits that either do not exist in the breed or could not be achieved easily through traditional breeding. This second kind of molecular intervention is an area of current research that still faces considerable uncertainties. Genome editing techniques, nevertheless, potentially offer a way to develop or accelerate the breeding of animals with agriculturally desirable characteristics and to exercise precise control over this at the molecular level.
Research is currently underway using genome editing to develop new features in a wide range of farmed animals including pigs, sheep, cattle and chickens. These applications include ones that could produce animals that are resistant to disease, that have higher proportions of muscle mass, are better adapted to environmental conditions, or can serve as surrogates to enable the births of greater numbers of productive offspring. Genome editing could also be used to produce ‘bioreactors’ – animals that produce pharmaceutical and other industrially valuable products.
Future genome editing technologies could help to increase food production sustainably in order to feed the growing world population, produce drugs that are otherwise difficult to source, or improve animal welfare. However, genome editing does not offer the only or a complete response to the challenges faced, and it could give rise to new concerns. These include concerns about product safety, consumer choice, and impacts on farmed animals, the environment and people (including the climate impacts of intensive meat and dairy farming).
[i] TALENs stands for ‘transcription activator-like effector nucleases’; CRISPR stands for ‘clustered regularly interspaced short palindromic repeats’ (Cas9 stands for ‘CRISPR associated protein 9’). These systems, and zinc finger nucleases (ZFNs), use endonucleases that operate as ‘molecular scissors’ to cut the DNA molecule at a desired point and exploit cell repair mechanisms to repair the cut using one of two pathways that are naturally present in all cells.
[ii] Refinements of the CRISPR system (e.g. so-called dCas-9) allow the modification of gene expression without cutting the DNA molecule (epigenetic modification). Base editing targets individual bases for enzymatic conversion and uses DNA mismatch repair mechanisms in the cell to exchange, for example, a C for a T or an A to a G, also without causing a Cas9-mediated double-stranded break in the DNA molecule.