CRISPR/Cas9 gene editing for genodermatoses: progress and perspectives

Abstract

Genodermatoses constitute a clinically heterogeneous group of devastating genetic skin disorders. Currently, therapy options are largely limited to symptomatic treatments and although significant advances have been made in ex vivo gene therapy strategies, various limitations remain. However, the recent technical transformation of the genome editing field promises to overcome the hurdles associated with conventional gene addition approaches. In this review, we discuss the need for developing novel treatments and describe the current status of gene editing for genodermatoses, focusing on a severe blistering disease called epidermolysis bullosa (EB), for which significant progress has been made. Initial research utilized engineered nucleases such as transcription activator-like effector nucleases and meganucleases. However, over the last few years, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) have upstaged older generation gene editing tools. We examine different strategies for CRISPR/Cas9 application that can be employed depending on the type and position of the mutation as well as the mode of its inheritance. Promising developments in the field of base editing opens new avenues for precise correction of single base substitutions, common in EB and other genodermatoses. We also address the potential limitations and challenges such as safety concerns and delivery efficiency. This review gives an insight into the future of gene editing technologies for genodermatoses.

Herbicide Resistance: Another Hot Agronomic Trait for Plant Genome Editing

“…Among all gene editing techniques, CRISPR-Cas9 systems are the most effective and widely deployed to induce trait improvement in crop plants including HR [ 39 , 40 ]. The latest advances in genome editing have led to unique CRISPR-Cas9 tools, such as base editing­, that is more precise, efficient, and a promising tool which enables targeted point mutations via nucleotide substitution in a programmable way [ 41 ]. The CRISPR-Cas systems, particularly the base editing, have potential to generate non-GM HR crops.…”

Clinical and molecular diagnosis of genodermatoses: Review and perspectives

“…Currently, the management of genodermatoses is primarily supportive. Continuously increasing our knowledge of genes responsible for genodermatoses appears paramount to further improving disease management, in parallel with the hope and promise of new gene therapies 86,87 …”

Cytosine Deaminase Base Editing to Restore COL7A1 in Dystrophic Epidermolysis Bullosa Human: Murine Skin Model

“…In addition, base editing is able to correct single nucleotide mutations with sufficient efficiency without the need for a positive selection of gene-corrected cells. In dystrophic epidermolysis bullosa, approximately 76% of registered mutations are single nucleotide mutations ( Naso and Petrova, 2019 ), and up to 61% of those can potentially be corrected with CBE or adenine base editor. Recently, adenine base editor−mediated base editing was successfully shown in primary RDEB fibroblasts and induced pluripotent stem cells (iPSCs) for two different COL7A1 nonsense mutations ( Osborn et al., 2020 ).…”