Genome Editing and precision medicine: promise and potential

CRISPR is a genome editing technique providing a way to induce targeted alterations in the DNA sequence, using proteins normally present in bacteria. This technique is proving to be fundamental in biomedicine as it is making it possible to investigate the molecular basis of some genetic diseases, but there are many fields in which it is used, in the agriculture and food sector, and in industry. We discussed this with Serena Zacchigna, Group leader of the Cardiovascular Biology Laboratory at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in Trieste.

How does CRISPR work?

CRISPR exploits a protein that is normally present in bacteria, making it possible to “cut and paste” the DNA sequence of a cell. These proteins are “guided” by small molecules of RNA which, besides carrying them to specific points in the DNA, indicate where the cut should be carried out. The cell’s DNA is therefore cut by this protein. At this point, there are two ways of repairing it: in one, the two strands are physically stitched together, which often entail errors in the joining and may disrupt the original DNA sequence: the other requires the use of an external template used by the cell to repair the DNA following a precise sequence which may not necessarily be present in the original DNA.

How can this technique be applied in biomedicine?

As this is a way to modify the DNA sequence, the main and most obvious use is clearly to correct mutations that occur spontaneously in the DNA of some individuals suffering from hereditary diseases. In the past, thanks to classical gene therapy, we were able to add genetic information to replace the missing one, but we were not able to correct the mutated sequences that were responsible for the diseased phenotype. Today, genome editing allows us to replace these faulty sequences with healthy ones. This technique may also lead to an exponential increase in the number of hereditary diseases that can be treated; in fact, by improving our knowledge of the genetic basis of many complex diseases, such as tumours, cardiovascular and neurodegenerative diseases, we will have a greater possibility of understanding how to use this genetic technique to interfere in the processes of development and progression of these diseases, by using genes as drugs.

Can CRISPR be used in the field of personalised medicine?

This technique is being used more and more to create experimental models to study diseases. CRISPR will allow us to recreate small organs from a patient’s stem cells. These organs will contain the patient’s specific genes and their cells will have specific mutations. Thanks to these models, we will be able not only to understand how the disease develops in the organ, but also to test various drugs to identify the most efficient one for each patient, bringing us ever closer to personalised medicine.

What differences are there between CRISPR and gene therapy?

There are two main differences between these techniques: the first is that CRISPR allows us to insert a genetic modification in a precise point, something which cannot be done with traditional gene therapy. Gene therapy is based on inserting an exogenous gene in a cell, but this does not allow us to integrate it into a specific site: in fact, if this exogenous sequence integrates into the cellular DNA in a point where important information is stored, further diseases could develop. The second difference is that in some cases, the modifications that are inserted by CRISPR could be reversible because, should the modification be found to be ineffective or even dangerous, the same technology can be used to return to the original sequence.

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