EBS in Children with De Novo Pathogenic Variants Disturbing .

Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents three pathogenic de novo variants in young children, with clinical manifestations appearing as early as the neonatal period. The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the gene, and indirect effects via pathogenic mutation in the gene, which interfere with the natural proteasome-mediated degradation pathway of KRT14.

Bridging Gaps in HDR Improvement: The Role of MAD2L2, SCAI, and SCR7.

This study aimed to enhance homology-directed repair (HDR) efficiency in CRISPR/Cas-mediated genome editing by targeting three key factors regulating the balance between HDR and non-homologous end joining (NHEJ): MAD2L2, SCAI, and Ligase IV. In order to achieve this, a cellular model using mutated eGFP was designed to monitor HDR events. Results showed that MAD2L2 knockdown and SCR7 treatment significantly improved HDR efficiency during Cas9-mediated HDR repair of the mutated eGFP gene in the HEK293T cell line.

[Genome Editing in Therapy of Genodermatoses].

This review is devoted to the prospects for the use of fundamentally important approaches and methods for the correction and therapy of genodermatoses, a group of inherited skin diseases. The greatest number of methods was applicable for the group of inherited epidermolysis bullosa. Gene replacement using viral and non-viral methods of delivery to cells has been replaced by genome editing using programmable nucleases used both in vitro and in vivo.

Rational Design of ssODN to Correct Mutations by Gene Editing.

Gene editing allows to make a variety of targeted changes in genome, which can potentially be used to treat hereditary human diseases. Despite numerous studies in this area, effectiveness of gene editing methods for correcting mutations is still low, so these methods are not allowed in routine practice. It has been shown that rational design of genome editing components can significantly increase efficiency of mutation correction.