Genome editing, also referred to as “gene editing”, “genome engineering” or “gene engineering”, encompasses various modern technologies that allow scientists to alter the DNA of organisms or cells. These techniques aim at inserting, removing, replacing or modifying specific fragments of DNA. Being able to “rewrite” DNA enables scientists to examine the consequences of these changes. For example, scientists might want to learn the effect of removing a specific gene, or want to investigate how a particular disease is caused.
Until recently, genome editing was difficult, expensive, and time consuming. However, the new CRISPR/Cas9 technique has meant that genome editing can be performed in laboratories all around the world. Highlighting the impact genome editing has had, the renowned scientific journal Science chose CRISPR/Cas9 as “Breakthrough of the Year” in 2015.
Genes, genomes and mutations
Cells in the body contain molecules of DNA, which carry all the information required for life. This information is divided into genes, and collectively, all the genes of an organism are as referred to as the organism’s genome. Chemically, molecules of DNA are long strings of smaller molecules called nucleotides. The order of these nucleotides – the DNA sequence – determines the information stored in genes.
To maintain healthy life the information stored in genes must be protected. However, DNA can be damaged by various factors, most notably exposure to the sun. DNA damage often takes the form of physical breaks in the DNA sequence, turning a long string of nucleotides into two shorter strings. In order to survive it is essential that DNA damage is repaired. The “default” repair mechanism simply re-joins the two molecules, but this is an error prone process and small mistakes are often made. So the combination of breaking and repairing DNA can cause small changes to the DNA sequence.
Small changes in the DNA sequence are referred to as mutations. Some mutations have little or no effect on the information stored in DNA, but others can cause a gene to be corrupted. At worst, the gene can be entirely inactivated and its information lost. The functional loss of a gene (i.e. it is still there but no longer works) is referred to as ‘gene knock-out’.
The genome editing process
The “basic” genome editing techniques take advantage of error-prone DNA repair mechanisms to knock-out a selected gene. The individual genome editing techniques have their own details, but their concepts are similar. In each case, special molecules called endonucleases act as “molecular scissors” to create a break in a cell or organism’s DNA. Scientists design the endonucleases to only cut the DNA at a location they have chosen, usually an important part of a gene of interest. If the endonuclease has been designed correctly, DNA will be cut but poorly repaired, with some nucleotides lost or gained. The result is the corruption of that gene.
But genome editing can do more than just knockout a gene. Scientists have learned how to change the information stored in DNA in more sophisticated ways. For example, tiny changes in the DNA sequence that might cause a disease can be made. Equally, disease-causing mutations can be ‘corrected’. Similarly to gene knockout, this more complicated genome editing also begins with the targeted cutting of DNA within a chosen gene, but the process of DNA repair is different. Scientists have learned how to activate an alternative DNA repair mechanism and trick it into making pre-planned mistakes. To do this, at the same time the endonuclease is added to the cells, a small piece of specially made DNA is also introduced. This DNA molecule has almost the same sequence as the gene that is being cut, but contains some minor differences that correspond to the mutation the scientist wants to make. Because the sequence of this DNA molecule is similar to that of the cell’s broken DNA, the cell sees the new DNA molecule as a template for what the correct repair should look like. If everything goes to plan, the cell will repair its damaged DNA, but will incorporate the desired mutation into the gene.
Genome editing is thus based on the use of engineered molecules that target and cut a specific site in a gene. By either allowing the cell to use its default repair mechanism that can cause the gene to be corrupted, or by tricking the cell into making an incorrect repair, almost any modification to the cell’s genome is possible. The applications are various, from understanding the function of a gene by generating genetically modified animals or cells, to gene therapy, drug research, and even agriculture. More importantly yet, the use of genome editing continues to grow and it is likely that these technologies will accelerate research, leading to important scientific breakthroughs in years to come.