Prime editing of hematopoietic stem cells (HSCs) has been used to rescue sickle cell disease (SCD) in an in vivo mouse model of SCD. In contrast to most other CRISPR-related approaches for SCD, the new method directly repair the disease-causing mutation in around 40% of HSCs after a single intravenous injection. After this procedure, on average, 43% of the malfunctioning HbS was replaced by normal HbA, significantly mitigating the SCD phenotypes.
A report in Molecular Therapy describes how high-fidelity RNA-targeting CRISPR-Cas13 can improve motor function in a mouse model of the rare neurodevelopmental disorder Angelman Syndrome (AS). The disease is caused by loss of function mutations in the maternally expressed gene UBE3A. In contrast, the intact and transcriptionally active, paternally inherited UBE3A is silenced by elongation of antisense long noncoding RNA UBE3A-ATS in neurons. Cas13-mediated suppression of the Ube3a-ATS lncRNA significantly alleviated AS-related symptoms, including obesity and motor function.
