Disruption of splice receptor sites of disease-associated genes using an adenosine deaminase base editor, including for treatment of hereditary diseases

摘要

The present invention features compositions and methods for treating, reducing or ameliorating the debilitating effects of amyotrophic lateral sclerosis (ALS) and spinal bulb muscular atrophy (SBMA). Herein, in conjunction with a guide polynucleotide, to disrupt the normal transcription of a gene associated with a hereditary disease or condition, e.g., ALS or SBMA, by modifying a target gene associated with the hereditary disorder or condition with a base editor system provided herein. Compositions and methods are provided that use improved novel base editors (eg, adenosine base editors) comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain.