Genome editing

The genetic manipulation of human stem and progenitor cells, either in a transient or permanent basis, opens a wide range of research possibilities that include the study of their biology as well as their use in the context of genome editing strategies aiming at treating, as of yet, incurable human disorders (“gene surgery”). From the plethora of methods available to introduce foreign nucleic acids into cells, those based on viral vectors are by far the most effective. Indeed, viruses have evolved a set of exquisite mechanisms to access and manipulate the inner workings of their host cells with the ultimate “purpose” of self-propagation.

Genome editing based on sequence-specific designer nucleases (a.k.a. programmable nucleases) permits “rewriting” the genetic information of living cells, including that inside the nucleus of human cells. The use of designer nucleases alone or together with donor DNA templates, which serve as surrogate homologous recombination substrates, can yield gene knockouts or gene knock-ins, respectively. Despite the fact that the main genome editing principles are well established, there are many crucial aspects linked to these targeted genetic modification technologies that, clearly, require further investigation. These aspects include devising improved methods for delivering the often large and complex genome editing tools into target cells; and increasing the specificity and fidelity of the knock-in procedures. In this regard, the deployment of viral vectors in genome editing settings is starting to shed light and address issues on both of these fronts (see Research Topics).