| First Author | Bose SK | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 4291 |
| PubMed ID | 34257302 | Mgi Jnum | J:313751 |
| Mgi Id | MGI:6725660 | Doi | 10.1038/s41467-021-24443-8 |
| Citation | Bose SK, et al. (2021) In utero adenine base editing corrects multi-organ pathology in a lethal lysosomal storage disease. Nat Commun 12(1):4291 |
| abstractText | In utero base editing has the potential to correct disease-causing mutations before the onset of pathology. Mucopolysaccharidosis type I (MPS-IH, Hurler syndrome) is a lysosomal storage disease (LSD) affecting multiple organs, often leading to early postnatal cardiopulmonary demise. We assessed in utero adeno-associated virus serotype 9 (AAV9) delivery of an adenine base editor (ABE) targeting the Idua G-->A (W392X) mutation in the MPS-IH mouse, corresponding to the common IDUA G-->A (W402X) mutation in MPS-IH patients. Here we show efficient long-term W392X correction in hepatocytes and cardiomyocytes and low-level editing in the brain. In utero editing was associated with improved survival and amelioration of metabolic, musculoskeletal, and cardiac disease. This proof-of-concept study demonstrates the possibility of efficiently performing therapeutic base editing in multiple organs before birth via a clinically relevant delivery mechanism, highlighting the potential of this approach for MPS-IH and other genetic diseases. |
