Correction of the pathogenic mutation in TGM1 gene by adenine base editing in mutant embryos.

A couple diagnosed as the carrier for Lamellar ichthyosis, an autosomal recessive rare disease, encountered two times pregnancy losses. Their blood samples showed the same heterozygous c.607C> T mutation in the TGM1 gene. However, we found about 98.4% of the sperm had mutations, suggesting possible de novo germline mutation. To explore the probability of correcting this mutation, we used two different adenine base editors combined with related truncated sgRNA to repair the pathogenic mutation in mutant zygotes. Our results showed the editing efficiency was 73.8% for ABEmax-NG combined with 20 bp-length sgRNA, and 78.7% for Sc-ABEmax combined with 19 bp-length sgRNA. The whole-genome sequencing and deep sequencing analysis demonstrated precise DNA editing. This study reveals the possibility of correcting the genetic mutation in embryos with the ABE system.