Figure 1.

Summary of recently explored strategies for targeted CRISPR/Cas9 gene engineering in cancer therapy. Targeted delivery of CRISPR/Cas9 system can be achieved by employing vectors, such as: certain Adeno-associated virus serotypes with tropism to various tissues; liposomes guided to cancerous cells by specific antibodies or their protein-free counterparts - aptamers; oncolytic viruses replicating preferably in cancer cells or extracellular vesicles covered with guiding molecules derived from parent cell. Targeted expression in cancerous tissue can be based on: miRNA switch with cancer-specific miRNA causing degradation of Cas9 mRNA; AND gate created with promoters specific to cancer and tissue-of-origin, controlling the expression of different elements of CRISPR/Cas9 system; telomerase activity dependency with Cas9 protein being expressed only in tissues with high telomerase activity (i.e. highly proliferating). Targeted modification of cancer-specific genes can either focus on: synthetic lethality (cell death induced by disruption of certain pair of genes, where disruption of only one of those genes exerts no damage to the cell) with CRISPR/Cas9 system targeting one gene with the second one already mutated in cancerous cells; targeting genes derived from oncogenic viruses that drive the tumorigenesis and are necessary for survival of cancer. (Graph created with BioRender.com (accessed on 23 November 2021)).