Improvements in the genetic editing technologies: CRISPR-Cas and beyond

Gene editing is a great hope not only for the scientific community, but also for society in general. This is due to its potential therapeutic applications that would allow curing diseases of genetic origin. The first realistic approach to achieve this goal was the development of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) tools. This review deals with some of the improvements that have been designed to obtain more efficient and safer genome editing. Initial CRISPR-Cas (CRISPR associated) editing systems yield low efficiency and undesired editing products. To solve these problems, new approaches emerged, such as the creation of base editors. Recent discoveries have led to the development of many interesting alternatives, such as the CRISPR-associated transposable systems, which open the range by generating guided insertions, or the discovery of other programmable nucleases like the IscB family, which greatly increase the range of proteins available for editing uses. Also, to address the limitations of base editors, prime editors were created; this novel system, despite having some disadvantages compared to base editor systems, has the potential to generate all the possible point mutations. On the other hand, dual prime editing systems (like twin and homologous 3' extension-mediated prime editors) have been developed to create targeted insertions and enhance the editing outcomes, respectively. Furthermore, advances in gene editing do not reside solely in CRISPR-dependent systems, as we will discuss when treating the Replication Interrupted Template-Driven DNA Modification technique.