Gene editing methods, systems, and compositions for treating spinal muscular atrophy

Abstract

The present disclosure provides methods for editing the SMN2 gene to increase the activity and / or amount and / or stability of SMN2 protein in a cell, thereby treating spinal muscular atrophy (SMA). Editing strategies utilizing both base editors and nucleases are provided herein. The present disclosure also provides guide RNAs for use in editing the SMN2 gene. Complexes comprising a base editor or a nuclease and any of the guide RNAs described herein are also provided. The present disclosure also provides nucleic acids, vectors, and viruses encoding the base editors or nucleases and guide RNAs provided herein, as well as kits comprising any of the guide RNAs and base editors or nucleases provided herein. Methods for treating SMA in a subject are also provided herein.

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