Progress in and Prospects of Genome Editing Tools for Human Disease Model Development and Therapeutic Applications

Abstract

Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas, are widely accepted because of their diversity and enormous potential for targeted genomic modifications in eukaryotes and other animals. Moreover, rapid advances in genome editing tools have accelerated the ability to produce various genetically modified animal models for studying human diseases. Given the advances in gene editing tools, these animal models are gradually evolving toward mimicking human diseases through the introduction of human pathogenic mutations in their genome rather than the conventional gene knockout. In the present review, we summarize the current progress in and discuss the prospects for developing mouse models of human diseases and their therapeutic applications based on advances in the study of programmable nucleases.

Keywords: genome editing; mouse model of human disease; programmable nuclease; therapeutic application.

Figure 1

Delivery strategies for gene editing using programmable nucleases in mice. The genome editors, including ZFNs, TALENs, CRISPR/Cas, PE, CBE, and ABE, can be delivered to mice using viral (AAVs and lentiviruses) or nonviral particles (SN, nanoparticles, and eVLPs) via microinjections or electroporation. In addition, the programmable nucleases can be directly delivered to mice using the i-GONAD method without any ex vivo modifications. ZFNs, zinc finger nucleases; TALENs, transcription activator-like effector nucleases; CRISPR, clustered regularly interspaced short palindromic repeats; Cas, CRISPR-associated protein; PE, prime editor; CBE, cytosine base editor; ABE, adenine base editor; AAVs, adeno-associated viral systems, SN, sponge-like silica nanoconstruct; eVLPs, engineered DNA-free virus-like particles; i-GONAD, improved genome editing via oviductal nucleic acid delivery. * This illustration was created with BioRender.com (accessed on 1 February 2023).