Application of Genome Editing Techniques in Immunology

Abstract

The idea of using the effector immune cells to specifically fight cancer has recently evolved into an exciting concept of adoptive cell therapies. Indeed, genetically engineered T cells expressing on their surface recombinant, cancer-targeted receptors have been shown to induce promising response in oncological patients. However, in addition to exogenous expression of such receptors, there is also a need for disruption of certain genes in the immune cells to achieve more potent disease-targeted actions, to produce universal chimeric antigen receptor-based therapies or to study the signaling pathways in detail. In this review, we present novel genetic engineering methods, mainly TALEN and CRISPR/Cas9 systems, that can be used for such purposes. These unique techniques may contribute to creating more successful immune therapies against cancer or prospectively other diseases as well.

Keywords: Adoptive therapy; CRISPR/Cas9; Cancer; Genome editing; Immunotherapy; TALEN; Viral diseases.

Fig. 1

Schematic representation of the double-strand DNA break introduction using TALEN. FokI enzyme acts as a catalytic domain following the recognition of specific DNA sequences by TALEs (depicted as colorful rectangles)

Fig. 2

Schematic representation of the double-strand DNA break introduction by a sgRNA-guided CRISPR/Cas9-based system and the main routes of DNA repairing. NHEJ non-homologous end joining, DSB double-strand breaks, HDR homology directed repair