Pathology Findings and In-Life Correlates in the Nonclinical Development of Adeno-Associated Virus (AAV)-Based Retinal Gene Therapies.

Adeno-associated virus (AAV)-based vectors are the most frequently used platform for retinal gene therapy. Initially explored for the treatment of loss-of-function mutations underpinning many inherited retinal diseases, AAV-based ocular gene therapies are increasingly used to transduce endogenous cells to produce therapeutic proteins, thus producing site-specific biofactories. Relatively invasive ocular routes of administration (ROA) mean prominent procedure-related in-life, and histopathological findings may be observed with some regularity.

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of Nonrodent Ocular Tissues.

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project (www.toxpath.org/ inhand.

Access to 2-Oxabicyclo[2.1.1]hexanes and their use in Scaffold Hopping.

Saturated isosteres of the -substituted benzene ring remain rare due to the paucity of methods to access complex bridged systems. Using blue-light-mediated [2 + 2] photocycloaddition chemistry, we have developed a quick and practical route to provide novel 2-oxabicyclo[2.1.

Discovery and Efficacy of AZ-PRMT5i-1, a Novel PRMT5 Inhibitor with High MTA Cooperativity.

PRMT5, a type 2 arginine methyltransferase, has a critical role in regulating cell growth and survival in cancer. With the aim of developing MTA-cooperative PRMT5 inhibitors suitable for MTAP-deficient cancers, herein we report our efforts to develop novel "MTA-cooperative" compounds identified through a high-throughput biochemical screening approach. Optimization of hits was achieved through structure-based design with a focus on improvement of oral drug-like properties.