Application of prime editing to the correction of mutations and phenotypes in adult mice with liver and eye diseases.
Nat Biomed Eng
; 6(2): 181-194, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-34446856
ABSTRACT
The use of prime editing-a gene-editing technique that induces small genetic changes without the need for donor DNA and without causing double strand breaks-to correct pathogenic mutations and phenotypes needs to be tested in animal models of human genetic diseases. Here we report the use of prime editors 2 and 3, delivered by hydrodynamic injection, in mice with the genetic liver disease hereditary tyrosinemia, and of prime editor 2, delivered by an adeno-associated virus vector, in mice with the genetic eye disease Leber congenital amaurosis. For each pathogenic mutation, we identified an optimal prime-editing guide RNA by using cells transduced with lentiviral libraries of guide-RNA-encoding sequences paired with the corresponding target sequences. The prime editors precisely corrected the disease-causing mutations and led to the amelioration of the disease phenotypes in the mice, without detectable off-target edits. Prime editing should be tested further in more animal models of genetic diseases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Eye Diseases
/
Gene Editing
Limits:
Animals
Language:
En
Journal:
Nat Biomed Eng
Year:
2022
Document type:
Article