PAM-flexible genome editing with an engineered chimeric Cas9

CRISPR enzymes require a defined protospacer adjacent motif (PAM) flanking a guide RNA-programmed target site, limiting their sequence accessibility for robust genome editing applications. In this study, we recombine the PAM-interacting domain of SpRY, a broad-targeting Cas9 possessing an NRN > NYN (R = A or G, Y = C or T) PAM preference, with the N-terminus of Sc + +, a Cas9 with simultaneously broad, efficient, and accurate NNG editing capabilities, to generate a chimeric enzyme with highly flexible PAM preference: SpRYc. We demonstrate that SpRYc leverages properties of both enzymes to specifically edit diverse PAMs and disease-related loci for potential therapeutic applications. In total, the approaches to generate SpRYc, coupled with its robust flexibility, highlight the power of integrative protein design for Cas9 engineering and motivate downstream editing applications that require precise genomic positioning

Androgenetic alopecia in women and men. italian guidelines adapted from european dermatology forum/european academy of dermatology and venereology guidelines

Androgenetic alopecia (AGA) is the most common form of alopecia, affecting up to 80% of men and 50% of women in the course of their life. AGA is caused by a progressive reduction in the diameter, length and pigmentation of the hair, resulting from the effects of the testosterone metabolite dihydrotestosterone (DHT) on androgen-sensitive hair follicles. Clinical presentation is different in men and women. Trichoscopy is used routinely in patients with androgenetic alopecia, for diagnosis and differential diagnosis with other diseases, allowing staging of severity and monitoring the progress of the disease and the response to treatment. Medical treatment of AGA includes topical minoxidil, antiandrogen agents, 5-alpha reductase inhibitors and many other options. This guideline for the treatment of androgenetic alopecia has been developed by an Italian group of experts taking into account the Italian pharmacological governance. The article is adapted from the original of the European Dermatology Forum (EDF) in collaboration with the European Academy of Dermatology and Venereology (EADV). It summarizes evidence-based and expert-based recommendations (S3 level)

Bullous pemphigoid: Italian guidelines adapted from the EDF/EADV guidelines

Bullous pemphigoid is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or generalized bullous lesions. In up to 20% of affected patients blister may be completely absent, and only excoriations, prurigo-like lesions, eczematous lesions, urticated lesions, and/or infiltrated plaques are observed. The disease is significantly associated with neurological disorders. The morbidity of bullous pemphigoid and its impact on the quality of life are significant. So far, a limited number of national treatment guidelines have been proposed, but no common European consensus has emerged. This guideline for the treatment of bullous pemphigoid has been developed by an Italian group of experts taking in account the Italian legislation and local pharmacological governance. Guidelines are adapted from the original article under the guidance of the European Dermatology Forum (EDF) in collaboration with the European Academy of Dermatology and Venereology (EADV). It summarizes evidence-based and expert-based recommendations (S2 level)